Publications by authors named "Heng Li"

980 Publications

Thulium Laser Resection of Bladder Tumors vs. Conventional Transurethral Resection of Bladder Tumors for Intermediate and High Risk Non-Muscle-Invasive Bladder Cancer Followed by Intravesical BCG Immunotherapy.

Front Surg 2021 8;8:759487. Epub 2021 Nov 8.

Department of Urology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Thulium laser resection of bladder tumors (TmLRBT) is recently considered as a common treatment option for non-muscle-invasive bladder cancers (NMIBC), but whether it is superior to Transurethral resection of bladder tumors (TURBT) are still undetermined. We retrospectively screened our institution database to identify patients who were treated by conventional TURBT or TmLRBT for NMIBC and followed by intravesical bacillus Calmette-Guérin (BCG) immunotherapy. The preoperative characteristics, perioperative outcomes, and recurrence-free survival were compared to assess the safety and efficacy of the two procedures. Eventually, 90 patients who underwent TmLRBT ( = 37) or TURBT ( = 53) followed by intravesical BCG immunotherapy were included. Two groups were similar in baseline characteristics except for the smaller tumor size of the TmLRBT group(1.7 cm vs. 2.2 cm; = 0.036). Obturator nerve reflex occurred in eight patients in the TURBT group and 3 of them suffered from bladder perforation while none happened in the TmLRBT group. The TmLRBT also had a shorter irrigation duration. In the multivariate Cox regression, the TmLRBT was related to less recurrence risk (HR: 0.268; 95% CI, 0.095-0.759; = 0.013). Our results suggested that TmLRBT is safer than conventional TURBT with fewer perioperative complications, and it offers better cancer control, therefore might be a superior option for NMIBC patients with intermediate and high recurrence risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fsurg.2021.759487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606824PMC
November 2021

A combination of bioinformatics analysis and rational design strategies to enhance keratinase thermostability for efficient biodegradation of feathers.

Sci Total Environ 2021 Nov 19:151824. Epub 2021 Nov 19.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, PR China. Electronic address:

Keratinase has shown great significance and application potentials in the biodegradation and recycle of keratin waste due to its unique and efficient hydrolysis ability. However, the inherent instability of the enzyme limits its practical utilization. Herein, we obtained a thermostability-enhanced keratinase based on a combination of bioinformatics analysis and rational design strategies for the efficient biodegradation of feathers. A systematical in silico analysis combined with filtering of virtual libraries derived a smart library for experimental validation. Synergistic mutations around the highly flexible loop, the calcium binding site and the non-consensus amino acids generated a dominant mutant which increased the optimal temperature of keratinase from 40 °C to 60 °C, and the half-life at 60 °C was increased from 17.3 min to 66.1 min. The mutant could achieve more than 66% biodegradation of 50 g/L feathers to high-valued keratin product with a major molecular weight of 36 kDa. Collectively, this work provided a promising keratinase variant with enhanced thermostability for efficient conversion of keratin wastes to valuable products. It also generated a general strategy to facilitate enzyme thermostability design which is more targeted and predictable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.151824DOI Listing
November 2021

Evaluation of Sleep Habits, Generalized Anxiety, Perceived Stress, and Research Outputs Among Postgraduate Research Students in Hong Kong During the Coronavirus (COVID-19) Pandemic.

J Multidiscip Healthc 2021 11;14:3135-3149. Epub 2021 Nov 11.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region.

Purpose: The current study aimed to evaluate the impact of coronavirus (COVID-19) pandemic on sleep hygiene, anxiety levels, perceived stress, and research output among postgraduate research students in Hong Kong.

Methods: An online survey was developed and distributed to Hong Kong postgraduate research students. The sleep hygiene, anxiety levels, and perceived stress during the outbreak of COVID-19 were assessed. Questions about COVID-19's impact on research outputs were asked.

Results: A total of 108 (response rate, 72%) full-time postgraduate students (PhD, 64%; M Phil, 8%; and Masters, 28%) participated. Approximately 83% of students reported poor sleep hygiene. Similarly, nearly 76% of students reported mild to severe levels of self-perceived anxiety levels. Most of the respondents (89%) expressed a moderate level of perceived stress. Sleep hygiene scores were moderately associated with anxiety levels (r = 0.384, p < 0.01) and perceived stress scores (r = 0.423, p < 0.01). Perceived stress was strongly correlated with anxiety levels (r = 0.601, p < 0.01). A hierarchical regression analysis revealed a significant association between respondents' ethnicity (B = -0.923, p = 0.003), past medical history (such as hypertension, diabetes, and musculoskeletal disorders) (B = 1.112, p = 0.005), or poor sleep hygiene (B = 0.259, p = 0.000) and high levels of perceived stress. Additionally, prior medical history (such as hypertension, diabetes, and musculoskeletal disorders) (B = 1.957, p = 0.001) and poor sleep hygiene (B = 0.312, p = 0.000) were found to be strongly related to anxiety levels among postgraduate research students.

Conclusion: This is the first study that highlights poor sleep hygiene, moderate-to-severe levels of anxiety, and perceived stress during the COVID-19 pandemic in postgraduate research students in Hong Kong. These findings will help educators to prepare strategies to alleviate the stress and psychological problems in postgraduate students.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JMDH.S325479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593900PMC
November 2021

Epigenetic glycosylation of SARS-CoV-2 impact viral infection through DC&L-SIGN receptors.

iScience 2021 Dec 11;24(12):103426. Epub 2021 Nov 11.

Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Glycosylation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein mediates viral entry and immune escape. While glycan site is determined by viral genetic code, glycosylation is completely dependent on host cell post-translational modification. Here, by producing SARS-CoV-2 virions from various host cell lines, viruses of different origins with diverse spike protein glycan patterns were revealed. Binding affinities to C-type lectin receptors (CLRs) DC&L-SIGN differed in the different glycan pattern virions. Although none of the CLRs supported viral productive infection, viral &cis-infection mediated by the CLRs were substantially changed among the different virions. Specifically, &cis-infection of virions with a high-mannose structure (ManGlcNAc) at the N1098 glycan site of the spike postfusion trimer were markedly enhanced. Considering L-SIGN co-expression with ACE2 on respiratory tract cells, our work underlines viral epigenetic glycosylation in authentic viral infection and highlights the attachment co-receptor role of DC&L-SIGN in SARS-CoV-2 infection and prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isci.2021.103426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582233PMC
December 2021

PVA-SM microstructure enhanced ratiometric fluorescence probe for formaldehyde detection in solution and gas.

Opt Lett 2021 Nov;46(22):5759-5762

Formaldehyde (FA) is one of the most common pollutants, which has tremendous harm to humans and environment. In this work, 4-amino-3-pentene-2-one (Fluoral-p) and coated quantum dot (@) were combined to implement a new ratiometric fluorescence probe @-Fluoral-p for FA detection. In addition, by utilization of polyvinyl alcohol (PVA) and microsphere (SM), a kind of PVA-SM microstructure was assembled with @-Fluoral-p to composite a signal enhanced sensing film. The @-Fluoral-p exhibited good response to 0-400 mg/L FA solution and an enhancement around 15 folds was realized after introducing PVA-SM. In both situations, the probe showed linear relationship to FA concentration (), with detection limits of 14 and 0.5 mg/L, respectively. Also, the sensing film showed a good linear response to FA gas in the range of 0 to 2 ppm, with a detection limit 0.03 ppm. As a result, the PVA-SM enhanced ratiometric fluorescence probe features high sensitivity, low detection limit, good selectivity, as well as portable, which can serve as a useful tool for investigating FA in solution and gas at room temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.441296DOI Listing
November 2021

Fast alignment and preprocessing of chromatin profiles with Chromap.

Nat Commun 2021 Nov 12;12(1):6566. Epub 2021 Nov 12.

Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.

As sequencing depth of chromatin studies continually grows deeper for sensitive profiling of regulatory elements or chromatin spatial structures, aligning and preprocessing of these sequencing data have become the bottleneck for analysis. Here we present Chromap, an ultrafast method for aligning and preprocessing high throughput chromatin profiles. Chromap is comparable to BWA-MEM and Bowtie2 in alignment accuracy and is over 10 times faster than traditional workflows on bulk ChIP-seq/Hi-C profiles and than 10x Genomics' CellRanger v2.0.0 pipeline on single-cell ATAC-seq profiles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-26865-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589834PMC
November 2021

An Analysis on Promoting Prefabrication Implementation in Construction Industry towards Sustainability.

Int J Environ Res Public Health 2021 10 31;18(21). Epub 2021 Oct 31.

Department of Civil Engineering, College of Engineering and Physical Sciences, Aston University, Birmingham B4 7ET, UK.

As a game-changing technology with significant environmental, economic, and social benefits, prefabricated technology has attracted attention and has been increasingly adopted in the construction industry. Although multitudinous studies have investigated various aspects of prefabrication in construction, a thorough review of its current development state that synthesized environmental, economic, and social sustainability dimensions remains overdue. Therefore, this study aims to fill this research gap by constructing a systematic framework, analyzing the research status quos, and providing recommendations for future research. This study first conducted a holistic review of 768 references with NVivo. A research foci framework that represented the body of knowledge in prefabrication in construction was developed with five levels, which were advantages, hindrances, stakeholders, promotion policies, and strategy spectrum. Following the framework, the in-depth analyses from the perspectives of environmental, economic, social sustainability, technologies development, and promotion strategies were performed. The current research domains were further linked with potential research directions for promoting prefabricated construction towards sustainability. The study is of value in both offering references for policy formulation and stakeholder practice and providing recommendations for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph182111493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583320PMC
October 2021

Propensity score-integrated power prior approach for augmenting the control arm of a randomized controlled trial by incorporating multiple external data sources.

J Biopharm Stat 2021 Nov 10:1-12. Epub 2021 Nov 10.

Division of Biostatistics, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.

In this paper, a propensity score-integrated power prior approach is developed to augment the control arm of a two-arm randomized controlled trial (RCT) with subjects from multiple external data sources such as real-world data (RWD) and historical clinical studies containing subject-level outcomes and covariates. The propensity scores for the subjects in the external data sources versus the subjects in the RCT are first estimated, and then subjects are placed in different strata based on their estimated propensity scores. Within each propensity score stratum, a power prior is formulated with the information contributed by the external data sources, and Bayesian inference on the treatment effect is obtained. The proposed approach is implemented under the two-stage study design framework utilizing the outcome-free principle to ensure the integrity of a study. An illustrative example is provided to demonstrate the implementation of the proposed approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10543406.2021.1998098DOI Listing
November 2021

A versatile platform for the tumor-targeted delivery of immune checkpoint-blocking immunoglobin G.

J Control Release 2021 Nov 6;340:243-258. Epub 2021 Nov 6.

Key Lab of Transplant Engineering and Immunology, MOH, West China Hospital, Sichuan University, Chengdu 610041, China; Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu 610041, China; Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Immunotherapies based on immune checkpoint-blocking antibodies have been considered the most attractive cancer treatments in recent years. However, the systemic administration of immune checkpoint-blocking antibodies is limited by low response rates and high risk of inducing immune-related adverse events (irAEs), which might be overcome by the tumor-targeted delivery of these antibodies. To achieve tumor-targeted delivery, immune checkpoint-blocking antibodies are usually modified with tumor-homing ligands through difficult genetic fusion or chemical conjugation. As most immune checkpoint-blocking antibodies are immunoglobin G (IgG) antibodies, we hypothesize that these IgG antibodies might be noncovalently modified with a tumor-homing ligand fused to an IgG-binding domain (IgBD). To test this hypothesis, the tumor-homing Z affibody, which targets platelet-derived growth factor receptor β (PDGFRβ), was fused to the Fab-selective IgBD in a trimeric format. After mixing Z fused to the IgBD with immune checkpoint-blocking IgG against programmed death-ligand 1 (αPD-L1), a novel homogenous complex was formed, indicating that αPD-L1 had been successfully modified with Z fused to the IgBD. Z-modified αPD-L1 bound to both PDGFRβ and PD-L1, thus leading to greater tumor uptake and antitumor effects in mice bearing PDGFRβPD-L1 tumor grafts. In addition, due to the broad spectrum of IgBD for IgG, immune checkpoint-blocking IgG antibodies against cytotoxic T-lymphocyte-associated protein 4 (αCTLA-4) and signal regulatory protein alpha (αSIRPα) were also modified with Z fused to the IgBD. These results demonstrated that a tumor-homing ligand fused to the IgBD might be developed as a versatile platform for the modification of immune checkpoint-blocking IgG antibodies to achieve tumor-targeted delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2021.11.003DOI Listing
November 2021

The roles of exosomal immune checkpoint proteins in tumors.

Mil Med Res 2021 Nov 8;8(1):56. Epub 2021 Nov 8.

Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.

Targeting immune checkpoints has achieved great therapeutic effects in the treatment of early-stage tumors. However, most patients develop adaptive resistance to this therapy. The latest evidence demonstrates that tumor-derived exosomes may play a key role in systemic immune suppression and tumor progression. In this article, we highlight the role of exosomal immune checkpoint proteins in tumor immunity, with an emphasis on programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as emerging evidence on roles of T cell immunoglobulin-3 (TIM-3), arginase 1 (ARG1), and estrogen receptor binding fragment-associated antigen 9 (EBAG9) expressed by exosomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40779-021-00350-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573946PMC
November 2021

Hierarchical Chiral Supramolecular Nanoarchitectonics with Molecular Detection: Helical Structure Controls upon Self-Assembly and Coassembly.

Macromol Rapid Commun 2021 Nov 7:e2100690. Epub 2021 Nov 7.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, China.

The morphological transformation from microspheres to helical supramolecular nanofibers with controllable handedness is achieved by the introduction of molecular chirality based on amino acid derivatives (TDAP), and the chirality of the supramolecular architectures that are achieved is nullified through the coassembly of the equivalent TDAP enantiomers. The molecular detection of achiral melamine based on the R-TDAP-COOH supramolecular system is achieved by the appearance of helicity and inversion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/marc.202100690DOI Listing
November 2021

Executive Summary of Clinical and Technical Guidelines for Esophageal Cancer Proton Beam Therapy From the Particle Therapy Co-Operative Group Thoracic and Gastrointestinal Subcommittees.

Front Oncol 2021 19;11:748331. Epub 2021 Oct 19.

Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, United States.

Radiation therapy (RT) is an integral component of potentially curative management of esophageal cancer (EC). However, RT can cause significant acute and late morbidity due to excess radiation exposure to nearby critical organs, especially the heart and lungs. Sparing these organs from both low and high radiation dose has been demonstrated to achieve clinically meaningful reductions in toxicity and may improve long-term survival. Accruing dosimetry and clinical evidence support the consideration of proton beam therapy (PBT) for the management of EC. There are critical treatment planning and delivery uncertainties that should be considered when treating EC with PBT, especially as there may be substantial motion-related interplay effects. The Particle Therapy Co-operative Group Thoracic and Gastrointestinal Subcommittees jointly developed guidelines regarding patient selection, treatment planning, clinical trials, and future directions of PBT for EC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.748331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560961PMC
October 2021

The emerging role of ISWI chromatin remodeling complexes in cancer.

J Exp Clin Cancer Res 2021 Nov 4;40(1):346. Epub 2021 Nov 4.

Department of Hematology, Institute of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Disordered chromatin remodeling regulation has emerged as an essential driving factor for cancers. Imitation switch (ISWI) family are evolutionarily conserved ATP-dependent chromatin remodeling complexes, which are essential for cellular survival and function through multiple genetic and epigenetic mechanisms. Omics sequencing and a growing number of basic and clinical studies found that ISWI family members displayed widespread gene expression and genetic status abnormalities in human cancer. Their aberrant expression is closely linked to patient outcome and drug response. Functional or componential alteration in ISWI-containing complexes is critical for tumor initiation and development. Furthermore, ISWI-non-coding RNA regulatory networks and some non-coding RNAs derived from exons of ISWI member genes play important roles in tumor progression. Therefore, unveiling the transcriptional regulation mechanism underlying ISWI family sparked a booming interest in finding ISWI-based therapies in cancer. This review aims at describing the current state-of-the-art in the role of ISWI subunits and complexes in tumorigenesis, tumor progression, immunity and drug response, and presenting deep insight into the physiological and pathological implications of the ISWI transcription machinery in cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-021-02151-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567610PMC
November 2021

Boosting Electrochemical Performance of Lithium-Rich Manganese-Based Cathode Materials through a Dual Modification Strategy with Defect Designing and Interface Engineering.

ACS Appl Mater Interfaces 2021 Nov 4;13(45):53974-53985. Epub 2021 Nov 4.

National Base for International Science & Technology Cooperation, National Local Joint Engineering Laboratory for Key Materials of New Energy Storage Battery, Hunan Province Key Laboratory of Electrochemical Energy Storage & Conversion, School of Chemistry, Xiangtan University, Xiangtan 411105, China.

Low Coulombic efficiency, severe capacity fading and voltage attenuation, and poor rate performance are currently great obstacles for the industrial application of lithium-rich manganese-based cathode materials (LRMCs) in lithium-ion batteries (LIBs). Herein, a dual modification strategy combining defect designing with interface engineering is reported to solve the above problems synchronously. Oxygen vacancies, a carbon nitride protective layer, and a fast ion conductor are simultaneously introduced in the LRMCs. It has been found that oxygen vacancies can suppress the release of irreversible oxygen, which is in favor of improving the initial Coulombic efficiency, the carbon nitride protective layer can improve the structural stability and alleviate the attenuation of capacity and voltage, and the fast ion conductor can promote the diffusion rate of Li and electron conductivity and thus enhance the rate capability. The modified material exhibits significantly enhanced electrochemical performances, including a favorable capacity retention rate of 94.2% over 120 cycles at 1C (1C = 200 mAh g) and excellent rate capabilities of 173.1 and 136.9 mAh g can be maintained at 5 and 10C after 100 cycles, respectively. Hence, the well-designed dual modification strategy with defect design and interface engineering provides significant exploration for the development and industrialization of LRMCs with high performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c16743DOI Listing
November 2021

Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity.

J Neuroinflammation 2021 Oct 26;18(1):244. Epub 2021 Oct 26.

Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.

Background: Diabetes mellitus (DM) is a common concomitant disease of late-onset myasthenia gravis (MG). However, the impacts of DM on the progression of late-onset MG were unclear.

Methods: In this study, we examined the immune response in experimental autoimmune myasthenia gravis (EAMG) rats with DM or not. The phenotype and function of the spleen and lymph nodes were determined by flow cytometry. The serum antibodies, Tfh cells, and germinal center B cells were determined by ELISA and flow cytometry. The roles of advanced glycation end products (AGEs) in regulating Tfh cells were further explored in vitro by co-culture assays.

Results: Our results indicated clinical scores of EAMG rats were worse in diabetes rats compared to control, which was due to the increased production of anti-R97-116 antibody and antibody-secreting cells. Furthermore, diabetes induced a significant upregulation of Tfh cells and the subtypes of Tfh1 and Tfh17 cells to provide assistance for antibody production. The total percentages of B cells were increased with an activated statue of improved expression of costimulatory molecules CD80 and CD86. We found CD4 T-cell differentiation was shifted from Treg cells towards Th1/Th17 in the DM+EAMG group compared to the EAMG group. In addition, in innate immunity, diabetic EAMG rats displayed more CXCR5 expression on NK cells. However, the expression of CXCR5 on NKT cells was down-regulated with the increased percentages of NKT cells in the DM+EAMG group. Ex vivo studies further indicated that Tfh cells were upregulated by AGEs instead of hyperglycemia. The upregulation was mediated by the existence of B cells, the mechanism of which might be attributed the elevated molecule CD40 on B cells.

Conclusions: Diabetes promoted both adaptive and innate immunity and exacerbated clinical symptoms in EAMG rats. Considering the effect of diabetes, therapy in reducing blood glucose levels in MG patients might improve clinical efficacy through suppressing the both innate and adaptive immune responses. Additional studies are needed to confirm the effect of glucose or AGEs reduction to seek treatment for MG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-021-02298-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549151PMC
October 2021

Identification of Potential Citrate Metabolism Pathways in .

Microorganisms 2021 Oct 18;9(10). Epub 2021 Oct 18.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiksberg, Denmark.

In the present study, we describe the identification of potential citrate metabolism pathways for the lactic acid bacterium (LAB) . A phenotypic assay indicated that four of six strains showed weak (Cm 6-1 and ATCC 35586) or even delayed (Cm 3-1 and Cm 5-1) citrate utilization activity. The remaining two strains, Cm 4-1 and Cm 1-2 gave negative results. Additional analysis showed no or very limited utilization of citrate in media containing 1% glucose and 22 or 30 mM citrate and inoculated with Cm 6-1 or ATCC 35586. Two potential pathways of citrate metabolism were identified by bioinformatics analyses in including either oxaloacetate (pathway 1) or tricarboxylic compounds such as isocitrate and α-ketoglutarate (pathway 2) as intermediates. Genes encoding pathway 1 were present in two out of six strains while pathway 2 included genes present in all six strains. The two potential citrate metabolism pathways in may potentially affect the sensory profiles of milk and soft cheeses subjected to growth with this species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms9102169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537297PMC
October 2021

Pathological changes in the lungs and lymphatic organs of 12 COVID-19 autopsy cases.

Natl Sci Rev 2020 Dec 29;7(12):1868-1878. Epub 2020 Sep 29.

Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents-findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1β). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nsr/nwaa247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543449PMC
December 2020

Identification of a novel IRF8 homozygous mutation causing neutrophilia, monocytopenia and fatal infection in a female neonate.

Infect Genet Evol 2021 Oct 16;96:105121. Epub 2021 Oct 16.

Department of Neonatology, First Hospital of Jilin University, Changchun 130021, China. Electronic address:

Inborn errors of immunity (IEIs) result from mutations in genes involved in host immune defense and immune regulation. Herein, we report the identification of a novel IRF8 mutation in a neonate with an IEI. DNA samples from both the neonate and her parents were subjected to DNA sequencing, and the immune status of the patient was assessed. We identified a mutation (c.331C > T, p. Arg111*) in the interferon regulatory factor 8 (IRF8) gene that manifested as sever dysfunctional neutrophilia (96.53 × 10/l) and monocytopenia (0.02 × 10/l). The patient's CD3 T cell and CD8 T cell counts were decreased. Her levels of IFN-γ were low even during severe infection. The mRNA expression levels of IRF8 were lower than normal. Her clinical manifestations included a recurrent and progressively fatal infection. Since IRF8 plays a key role in the differentiation and development of immune cells, we suspected that the novel mutation (c.331C > T, p. Arg111*) may be consistent with a severe loss of IRF8 function and result in a failure of immune cells to differentiate and maturation, and lead to a severe infection with early onset.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2021.105121DOI Listing
October 2021

Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.

Microbiol Spectr 2021 10 13;9(2):e0135221. Epub 2021 Oct 13.

Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen Universitygrid.12981.33, Zhuhai, China.

The emerging new lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have marked a new phase of coronavirus disease 2019 (COVID-19). Understanding the recognition mechanisms of potent neutralizing monoclonal antibodies (NAbs) against the spike protein is pivotal for developing new vaccines and antibody drugs. Here, we isolated several monoclonal antibodies (MAbs) against the SARS-CoV-2 spike protein receptor-binding domain (S-RBD) from the B cell receptor repertoires of a SARS-CoV-2 convalescent. Among these MAbs, the antibody nCoV617 demonstrates the most potent neutralizing activity against authentic SARS-CoV-2 infection, as well as prophylactic and therapeutic efficacies against the human angiotensin-converting enzyme 2 (ACE2) transgenic mouse model . The crystal structure of S-RBD in complex with nCoV617 reveals that nCoV617 mainly binds to the back of the "ridge" of RBD and shares limited binding residues with ACE2. Under the background of the S-trimer model, it potentially binds to both "up" and "down" conformations of S-RBD. mutagenesis assays show that mutant residues found in the emerging new lineage B.1.1.7 of SARS-CoV-2 do not affect nCoV617 binding to the S-RBD. These results provide a new human-sourced neutralizing antibody against the S-RBD and assist vaccine development. COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It contains a variety of dominant neutralizing epitopes and is an important antigen for the development of new coronavirus antibodies. The significance of our research lies in the determination of new epitopes, the discovery of antibodies against RBD, and the evaluation of the antibodies' neutralizing effect. The identified antibodies here may be drug candidates for the development of clinical interventions for SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/Spectrum.01352-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515945PMC
October 2021

New strategies to improve minimap2 alignment accuracy.

Authors:
Heng Li

Bioinformatics 2021 Oct 8. Epub 2021 Oct 8.

Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA.

Summary: We present several recent improvements to minimap2, a versatile pairwise aligner for nucleotide sequences. Now minimap2 v2.22 can more accurately map long reads to highly repetitive regions and align through insertions or deletions up to 100kb by default, addressing major weakness in minimap2 v2.18 or earlier.

Availability And Implementation: https://github.com/lh3/minimap2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btab705DOI Listing
October 2021

Comparison of different methods of nasogastric tube insertion in anesthetized and intubated patients: A meta-analysis.

World J Clin Cases 2021 Sep;9(26):7772-7785

Department of Anesthesiology, Qingyuan People's Hospital, The Six Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China.

Background: Several techniques of nasogastric tube (NGT) insertion have been described in the literature with different success rates.

Aim: To systematically search the literature and conduct a meta-analysis comparing the success rates, insertion time and complications associated with different techniques of NGT insertion in anesthetized and intubated patients.

Methods: An electronic search of the PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar databases were performed up to October 31, 2019. We included 17 randomized controlled trials with 2500 participants in the meta-analysis.

Results: As compared to the conventional method, successful insertion of the NGT on first attempt was higher with modified techniques such as the reverse Sellick's maneuver [relative risk (RR) 1.94; 95% confidence interval (CI): 1.62-2.31], use of a frozen NGT (RR 1.55; 95%CI: 1.13-2.13), inserting the NGT with neck flexion and lateral neck pressure (RR 1.64; 95%CI: 1.10-2.45), endotracheal tube-assisted (RR 1.88; 95%CI: 1.52-2.32) and video-assisted placements (RR 1.60; 95%CI: 1.31-1.95). All the modified techniques also led to comparatively higher insertion success rates than the conventional technique.

Conclusion: The use of modified techniques of NGT insertion such as the reverse Sellick's maneuver, neck flexion with lateral neck pressure, frozen NGT, endotracheal tube-guided or video-assisted methods result in a significantly better chance of successful tube insertion at first attempt as compared to the conventional technique. All modified techniques also significantly improve the overall chance of successful NGT placement as compared to the conventional method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v9.i26.7772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462255PMC
September 2021

Effects of task complexity or rate of motor imagery on motor learning in healthy young adults.

Brain Behav 2021 Nov 6;11(11):e02122. Epub 2021 Oct 6.

Department of Building and Real Estate, Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region.

Background: A growing body of evidence suggests the benefit of motor imagery in motor learning. While some studies tried to look at the effect of isolated mental practice, others evaluated the combined effect of motor imagery and physical practice in clinical rehabilitation. This study aimed to investigate the effects of task complexity or rates of motor imagery on motor learning in health young adults.

Methods: Eighty-eight healthy individuals participated in this study. Participants were randomly allocated to either Group A (50% complex, N = 22), Group B (75% complex, N = 22), Group C (50% simple, N = 22), or Group D (75% simple, N = 22). Participants in the complex groups performed their task with nondominant hand and those in simple groups with a dominant hand. All participants performed a task that involved reach, grasp, and release tasks. The performance of the four groups was examined in the acquisition and retention phase. The main outcome measure was the movement time.

Results: There were significant differences between immediate (i.e., acquisition) and late (i.e., retention) movement times at all three stages of task (i.e., MT [reaching time], MT [target transport time], and TMT [reaching time plus object transport time]) when individuals performed complex task with 75% imagery rate (p < .05). Similarly, there were significant differences between immediate and late movement times at all stages of task except the MT when individuals performed simple task with 75% imagery rate (p < .05). There were significant effects of task complexity (simple vs. complex tasks) on immediate movement time at the first stage of task (i.e., MT ) and late movement times of all three stages of task (p < .05). There were significant effects of the rate of imagery (50% vs. 75%) on late movement times at all three stages of tasks (p > .05). Additionally, there were no interaction effects of either task complexity or rate of imagery on both immediate and late movement times at all three stages of tasks (p > .05).

Conclusion: This study supports the use of higher rates (75%) of motor imagery to improve motor learning. Additionally, the practice of a complex task demonstrated better motor learning in healthy young adults. Future longitudinal studies should validate these results in different patient's population such as stroke, spinal cord injury, and Parkinson's disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/brb3.2122DOI Listing
November 2021

The potent radioprotective agents: Novel nitronyl nitroxide radical spin-labeled resveratrol derivatives.

Fitoterapia 2021 Nov 2;155:105053. Epub 2021 Oct 2.

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

It is commonly known that radiotherapy is still a key modality for treatment of cancer. Though this effect is desirable during radiotherapy, it leads to radiotoxicity on normal healthy cells. In the present research, we designed, synthesized and analyzed a series of nitronyl nitroxide radical (NITR) spin-labeled resveratrol (RES) derivatives. The cytotoxicity of the newly synthesized substances was tested on Jurkat T cells. The derivatives were studied as reactive oxygen species (ROS) scavenger to protect ionizing radiation of Jurkat T cells upon 6 Gy X-irradiation. The experimental results revealed that compound 2 and 3 could significantly alleviate the damage of Jurkat T cells, as evidenced by decreasing ROS production and restoring the cell apoptosis. Further mechanism investigations indicated that the radioprotective effects of the novel derivatives were largely associated with modulating the expression of apoptotic proteins including cIAP-1, cIAP-2, cytochrome c, caspase-3 and caspase-9. Based on the experimental result, we disclosed that the novel NITR spin-labeled RES derivatives exhibit the potential to be used as the novel radioprotective candidates to ameliorate the injury induced by ionizing radiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2021.105053DOI Listing
November 2021

Palladium(II)-Catalyzed Dehydrogenative Strategy for Direct and Regioselective Oligomerization of BODIPY Dyes.

Org Lett 2021 Oct 4;23(20):7986-7991. Epub 2021 Oct 4.

Anhui Laboratory of Molecule-Based Materials, The Key Laboratory of Functional Molecular Solids, Ministry of Education, School of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, China.

A family of directly β,γ-linked BODIPY oligomers up to pentamers were regioselectively prepared via Pd(II)-catalyzed oxidative C-H cross-coupling. The structural integrity of β,γ-linked dimers was unambiguously confirmed by X-ray crystallography. These structurally unprecedented oligomers showed red-shifted absorptions and near-infrared emissions along with efficient intersystem crossing, giving Φ in the range of 12-43%, for potential use as heavy-atom-free photosensitizers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c02996DOI Listing
October 2021

Identification of phosphodiesterase-4 as the therapeutic target of arctigenin in alleviating psoriatic skin inflammation.

J Adv Res 2021 11 4;33:241-251. Epub 2021 Mar 4.

Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Introduction: Arctigenin, derived from Arctium lappa L., has multiple pharmacological activities, including immunoregulatory, anti-diabetic, anti-tumor, and neuroprotective effects. Nevertheless, the potential therapeutic target of arctigenin in modulating inflammation remains undefined.

Objectives: In the present study, we identified that arctigenin was a phosphodiesterase-4 (PDE4) selective inhibitor for the first time. Further investigations were performed to fully uncover the effects and mechanism of arctigenin on experimental murine psoriasis model.

Methods: Crystal structure determination, PDEs enzyme assay, and isothermal titration calorimetry were included to illustrate the binding specialty, inhibitory effects, and selectivity of arctigenin on PDE4D. The anti-inflammatory effects were conducted in LPS-activated human peripheral blood mononuclear cells (PBMCs) and RAW264.7 cells. Imiquimod-induced murine psoriasis was performed to uncover the therapeutic effects and mechanism of arctigenin .

Results: Arctigenin could bind to the catalytic domain of PDE4D via formation of hydrogen bonds as well as π-π stacking interactions between the dibenzyl butyrolactone of arctigenin and several residues of PDE4D. Accordingly, arctigenin showed prominent anti-inflammation in human PBMCs and murine RAW264.7 cells. PDE4 inhibition by arctigenin resulted in elevation of intracellular cyclic adenosine monophosphate (cAMP) and phosphorylation of cAMP-response element binding protein (CREB), which were largely blocked through intervention of protein kinase A (PKA) activity by H89 treatment or reduction of protein expression by siRNA transfection. Moreover, we first identified that a topical application of arctigenin ameliorated experimental psoriatic manifestations in imiquimod-induced murine psoriasis model by decreasing adhesion and chemotaxis of several inflammatory cells. Further proteomics analysis revealed that arctigenin could rectify the immune dysfunction and hyperactivation of keratinocytes in the inflamed skin microenvironments, which might be largely related to the expression of Keratins.

Conclusion: The research provided credible clew that inhibition of PDE4 by arctigenin might function as the potential therapeutic approach for the treatment of psoriasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jare.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463927PMC
November 2021

Thermal-Responsive and Fire-Resistant Materials for High-Safety Lithium-Ion Batteries.

Small 2021 10 27;17(43):e2103679. Epub 2021 Sep 27.

Institute of Applied Physics and Materials Engineering, Joint Key Laboratory of the Ministry of Education, University of Macau, Avenida da Universidade, Taipa, Macau, SAR, 999078, P. R. China.

As one of the most efficient electrochemical energy storage devices, the energy density of lithium-ion batteries (LIBs) has been extensively improved in the past several decades. However, with increased energy density, the safety risk of LIBs becomes higher too. The frequently occurred battery accidents worldwide remind us that safeness is a crucial requirement for LIBs, especially in environments with high safety concerns like airplanes and military platforms. It is generally recognized that the catastrophic thermal runaway (TR) event is the major cause of LIBs related accidents. Tremendous efforts have been devoted to coping with the TR concerns in LIBs, and thus enhance battery safety. This review first gives an introduction to the fundamentals of LIBs and the origins of safety issues. Then, the authors summarize the recent advances to improve the safety of LIBs with a unique focus on thermal-responsive and fire-resistant materials. Finally, a perspective is proposed to guide future research directions in this field. It is anticipated this review will stimulate inspiration and arouse extensive studies on further improvement in battery safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/smll.202103679DOI Listing
October 2021

HO-Mediated Oxidative Stress Enhances Cystathionine γ-Lyase-Derived HS Synthesis via a Sulfenic Acid Intermediate.

Antioxidants (Basel) 2021 Sep 18;10(9). Epub 2021 Sep 18.

School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.

Hydrogen sulfide (HS), which is generated mainly by cystathionine -lyase (CSE) in the cardiovascular system, plays a pivotal role in a wide range of physiological and pathological processes. However, the regulatory mechanism of the CSE/HS system is poorly understood. Herein, we show that oxidation induces the disulfide bond formation between Cys252 and Cys255 in the CXXC motif, thus stimulating the HS-producing activity of CSE. The activity of oxidized CSE is approximately 2.5 fold greater than that of the reduced enzyme. Molecular dynamics and molecular docking suggest that the disulfide bond formation induces the conformational change in the active site of CSE and consequently increases the affinity of the enzyme for the substrate L-cysteine. Mass spectrometry and mutagenesis studies further established that the residue Cys255 is crucial for oxidation sensing. Oxidative stress-mediated sulfenylation of Cys255 leads to a sulfenic acid intermediate that spontaneously forms an intramolecular disulfide bond with the vicinal thiol group of Cys252. Moreover, we demonstrate that exogenous hydrogen peroxide (HO) and endogenous HO triggered by vascular endothelial growth factor (VEGF) promote cellular HS production through the enhancement of CSE activity under oxidative stress conditions. By contrast, incubation with HO or VEGF did not significantly enhance cellular HS production in the presence of PEG-catalase, an enzymatic cell-permeable HO scavenger with high HO specificity. Taken together, we report a new posttranslational modification of CSE that provides a molecular mechanism for HO/HS crosstalk in cells under oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox10091488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466214PMC
September 2021

Leveraging real-world evidence for determining performance goals for medical device studies.

Stat Med 2021 Dec 24;40(29):6577-6589. Epub 2021 Sep 24.

Division of Biostatistics, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.

Performance goals are numerical target values pertaining to effectiveness or safety endpoints in single-arm medical device clinical studies. Typically, performance goals are determined at the planning stage of the investigational study under consideration based on summarized outcome information from existing relevant clinical trials. In recent years, there is a growing interest in leveraging real-world evidence in medical product development. In this article, we introduce a new method for proposing performance goals by leveraging real-world evidence. The method applies entropy balancing to address possible patient dissimilarities between the study's target patient population and existing real-world patients, and can take into account operation differences between clinical studies and real-world clinical practice. An illustrative example is provided to demonstrate how to implement the proposed method for performance goal determination while leveraging real-world evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/sim.9199DOI Listing
December 2021
-->