Publications by authors named "Li Peng"

4,496 Publications

  • Page 1 of 1

Thermally Activated Delayed Fluorescence Enabled by Reversed Conformational Distortion for Blue Emitters.

J Phys Chem Lett 2021 Sep 24:9501-9507. Epub 2021 Sep 24.

Department of Chemistry, Molecular Dynamic Chemistry Center, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, School of Science, Tianjin University, Tianjin 300354, China.

In this work, we present for the first time a general strategy via molecular reversed conformational distortion for thermally activated delayed fluorescence (TADF). A model purely organic compound named BNNIO with a common fluorophore flexibly linked to benzene by an oxygen atom is rationally designed and successfully synthesized. Moreover, the rate constant of reverse intersystem crossing reaches 2.34 × 10 s as determined by transient spectroscopy. As a result, TADF emission of BNNIO is observed with a photoluminescence quantum yield of 90.72% and a lifetime of 84.76 μs at 415 nm. This universal regulation strategy undoubtedly opens a new avenue for the development of novel purely organic blue light-emitting materials.
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http://dx.doi.org/10.1021/acs.jpclett.1c02642DOI Listing
September 2021

Association of poor sleep burden in middle age and older adults with risk for delirium during hospitalization.

J Gerontol A Biol Sci Med Sci 2021 Sep 24. Epub 2021 Sep 24.

Medical Biodynamics Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.

Background: Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization.

Methods: 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype-a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first.

Results: In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p<0.001) and 57% (1.57 [1.38-1.80], p<0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction <0.001).

Conclusion: Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.
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http://dx.doi.org/10.1093/gerona/glab272DOI Listing
September 2021

Embryo-Engineered Nonhuman Primate Models: Progress and Gap to Translational Medicine.

Research (Wash D C) 2021 21;2021:9898769. Epub 2021 Aug 21.

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China.

Animal models of human diseases are vital in better understanding the mechanism of pathogenesis and essential for evaluating and validating potential therapeutic interventions. As close relatives of humans, nonhuman primates (NHPs) play an increasingly indispensable role in advancing translational medicine research. In this review, we summarized the progress of NHP models generated by embryo engineering, analyzed their unique advantages in mimicking clinical patients, and discussed the remaining gap between basic research of NHP models to translational medicine.
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http://dx.doi.org/10.34133/2021/9898769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404551PMC
August 2021

Discovery and Preclinical Pharmacology of an Oral Bromodomain and Extra-Terminal (BET) Inhibitor Using Scaffold-Hopping and Structure-Guided Drug Design.

J Med Chem 2021 Sep 20. Epub 2021 Sep 20.

Research and Development, Bristol Myers Squibb Company, P. O. Box 4000, Princeton, New Jersey 08543-4000, United States.

Inhibition of the bromodomain and extra-terminal (BET) family of adaptor proteins is an attractive strategy for targeting transcriptional regulation of key oncogenes, such as c-MYC. Starting with the screening hit , a combination of structure-activity relationship and protein structure-guided drug design led to the discovery of a differently oriented carbazole with favorable binding to the tryptophan, proline, and phenylalanine (WPF) shelf conserved in the BET family. Identification of an additional lipophilic pocket and functional group optimization to optimize pharmacokinetic (PK) properties culminated in the discovery of (BMS-986158) with excellent potency in binding and functional assays. On the basis of its favorable PK profile and robust in vivo activity in a panel of hematologic and solid tumor models, BMS-986158 was selected as a candidate for clinical evaluation.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00625DOI Listing
September 2021

The perinatal outcomes of frozen-thawed blastocyst transfer are better than fresh blastocyst transfer: a systematic review and meta-analysis.

Ginekol Pol 2021 Sep 20. Epub 2021 Sep 20.

Objectives: Transfer of cryopreserved-warmed blastocysts is common in the practice of in vitro fertilization. The purpose of the study is to examine the available evidence and determine whether cryopreservation of blastocysts and subsequent frozen blastocyst transfer (BT) result in better outcomes than fresh BT.

Material And Methods: Related studies comparing outcomes of in vitro fertilization (IVF) cycles between fresh and frozen BTs were retrieved from Medline, Cochrane Central Register of Clinical Trials, EMBASE, DARE, and CINAHL through March 2020. The outcomes of interest were preterm birth, extremely preterm birth, small for gestational age, large for gestational age, low birth weight, extremely low birth weight, caesarean section, perinatal mortality and preeclampsia. The analysis was performed using Rev Man 5.1 software. Risk ratios (RRs) and risk differences were calculated with 95% confidence intervals, to evaluate the results of each outcome. The quality of the referenced studies was assessed using the Newcastle-Ottawa scale (NOS) checklists.

Results: Nine studies with 42,342 women incorporated in this meta-analysis. The incidence of preterm birth (RR = 0.89, 95% CI: 0.82, 0.97) and small for gestational age (RR = 0.55, 95% CI 0.41-0.74) was low in frozen BT group. There was no significant difference in the risk of low birth weight (RR = 0.89, 95% CI: 0.67, 1.19) and perinatal mortality (RR = 1.47, 95% CI: 0.85, 2.55) between frozen-thawed and fresh BT. Singleton pregnancy after frozen BT was associated with higher large for gestational age (RR = 1.47, 95% CI: 1.37, 1.57), caesarean section rates (RR = 1.24, 95% CI: 1.13, 1.36) and preeclampsia compared with fresh BT (RR = 1.85, 95% CI: 1.22, 2.82).

Conclusions: The frozen BT results in better perinatal outcomes compared with that of fresh BT. Furthermore, comprehensive randomized clinical trials comparing freeze-all with fresh BT cycles are needed to draw sound conclusions.
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http://dx.doi.org/10.5603/GP.a2021.0159DOI Listing
September 2021

Rictor Activates Cav 1 Through the Akt Signaling Pathway to Inhibit the Apoptosis of Gastric Cancer Cells.

Front Oncol 2021 1;11:641453. Epub 2021 Sep 1.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China.

Background: Rapamycin-insensitive companion of mammalian target of rapamycin (Rictor) protein is a core subunit of mammalian target of rapamycin complex 2, and is associated with cancer progression. However, the biological function of Rictor in cancer, particularly its clinical relevance in gastric cancer (GC) remains largely unknown.

Methods: Rictor expression and its association with clinicopathologic characteristics in GC were analyzed by immunohistochemistry. Effect of Rictor and Caveolin-1 (Cav 1) on GC cells apoptosis was evaluated overexpression experiment . Mechanisms of Rictor and Cav 1 in GC were explored through overexpression and knockdown, by immunofluorescence and western blot analyses.

Results: Rictor was upregulated in GC, and mainly located in the cytoplasm of cancer cells. Moreover, higher Rictor levels were associated with worse prognosis. Rictor could inhibit GC cell apoptosis and promote cell growth . The results of immunofluorescence revealed that Cav 1 localized in GC cell membrane but did not co-localize with Rictor. Further, Rictor regulated apoptosis-related proteins, long non-coding RNAs and also activated cellular signaling, thereby positively regulating Cav 1 expression. This effect was attenuated by the Akt inhibitor ly294002. Cav 1 did not significantly affect the ability of Rictor to inhibit tumor cell apoptosis.

Conclusions: Rictor is upregulated in GC and associated with worse prognosis. It inhibits tumor apoptosis and activates Cav 1 through the Akt signaling pathway to inhibit the apoptosis of GC cells. Rictor is, therefore, a promising prognostic biomarker and possible therapeutic target in GC patients.
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http://dx.doi.org/10.3389/fonc.2021.641453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442624PMC
September 2021

Rictor Activates Cav 1 Through the Akt Signaling Pathway to Inhibit the Apoptosis of Gastric Cancer Cells.

Front Oncol 2021 1;11:641453. Epub 2021 Sep 1.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China.

Background: Rapamycin-insensitive companion of mammalian target of rapamycin (Rictor) protein is a core subunit of mammalian target of rapamycin complex 2, and is associated with cancer progression. However, the biological function of Rictor in cancer, particularly its clinical relevance in gastric cancer (GC) remains largely unknown.

Methods: Rictor expression and its association with clinicopathologic characteristics in GC were analyzed by immunohistochemistry. Effect of Rictor and Caveolin-1 (Cav 1) on GC cells apoptosis was evaluated overexpression experiment . Mechanisms of Rictor and Cav 1 in GC were explored through overexpression and knockdown, by immunofluorescence and western blot analyses.

Results: Rictor was upregulated in GC, and mainly located in the cytoplasm of cancer cells. Moreover, higher Rictor levels were associated with worse prognosis. Rictor could inhibit GC cell apoptosis and promote cell growth . The results of immunofluorescence revealed that Cav 1 localized in GC cell membrane but did not co-localize with Rictor. Further, Rictor regulated apoptosis-related proteins, long non-coding RNAs and also activated cellular signaling, thereby positively regulating Cav 1 expression. This effect was attenuated by the Akt inhibitor ly294002. Cav 1 did not significantly affect the ability of Rictor to inhibit tumor cell apoptosis.

Conclusions: Rictor is upregulated in GC and associated with worse prognosis. It inhibits tumor apoptosis and activates Cav 1 through the Akt signaling pathway to inhibit the apoptosis of GC cells. Rictor is, therefore, a promising prognostic biomarker and possible therapeutic target in GC patients.
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http://dx.doi.org/10.3389/fonc.2021.641453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442624PMC
September 2021

Seroprevalence of coxsackievirus A16 antibody among people of various age groups: a systematic review and meta-analysis.

Arch Public Health 2021 Sep 17;79(1):166. Epub 2021 Sep 17.

Zhoushan Municipal Center for Disease Control and Prevention, No.568 Wengshan Road, Zhoushan City, Zhejiang Province, 316021, People's Republic of China.

Background: Coxsackie virus group A type 16 (CoxA16) is the main pathogen and usually an alternative to or joins in prevalence with enterovirus 71 (EV71) causing hand, foot and mouth disease (HFMD). The objective of this study was to estimate the seroprevalence of CoxA16 antibody among people of various age groups by a systematic review and meta-analysis.

Methods: The literature of seroprevalence of CoxA16 antibody among people has been systematically searched through databases from the date of their establishment to Jan. 2021. Estimates of seroprevalence of CoxA16 antibody by gender and age groups have been summarized by using fixed- and random- effect models. All analyses have been conducted in STATA version 12.0 software.

Results: A total of 14 publications with 9 in English and 5 in Chinese containing 9562 samples were finally included in the meta-analysis. The seroprevalence of CoxA16 antibody reported in different studies range from 24.85 to 76.92 %. Meta-analysis has revealed that the seroprevalence of CoxA16 antibody was 56.3 % (95 %CI: 47.7 %~64.9 %) in the overall population and 55.1 % (95 %CI: 44.1 %~66.1 %) in the Chinese population. Subgroup analysis by gender has revealed that the seroprevalence of CoxA16 antibody was 56.1 % (95 %CI: 45.2 %~67.1 %) in males and 60.0 % (95 %CI: 50.0 %~69.9 %) in females. Subgroup analysis by age groups has revealed that the seroprevalence of CoxA16 antibody was 49.1 % (95 %CI: 36.2 %~62.0 %) in the 0 ~ 5 age group and 63.9 % (95 %CI: 53.1 %~74.7 %) in the over 5 age group. Begg's funnel plots have suggested that there were no publication bias in all groups. Sensitive analysis has suggested that the result of the meta-analysis was stable.

Conclusions: The seroprevalence of CoxA16 antibody was closely related to age. Children under 5 years old were the main susceptible groups for CoxA16 and also the key groups for the prevention and control of HFMD.
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http://dx.doi.org/10.1186/s13690-021-00688-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447778PMC
September 2021

Influence of viral transport media and freeze-thaw cycling on the sensitivity of qRT-PCR detection of SARS-CoV-2 nucleic acids.

Nanoscale 2021 Sep 17. Epub 2021 Sep 17.

School of Chemistry and Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Republic of Ireland.

: The events of the last year have highlighted the complexity of implementing large-scale molecular diagnostic testing for novel pathogens. The purpose of this study was to determine the chemical influences of sample collection media and storage on the stability and detection of viral nucleic acids by qRT-PCR. We studied the mechanism(s) through which viral transport media (VTM) and number of freeze-thaw cycles influenced the analytical sensitivity of qRT-PCR detection of SARS-CoV-2. Our goal is to reinforce testing capabilities and identify weaknesses that could arise in resource-limited environments that do not have well-controlled cold chains. : The sensitivity of qRT-PCR analysis was studied in four VTM for synthetic single-stranded RNA (ssRNA) and double-stranded DNA (dsDNA) simulants of the SARS-CoV-2 genome. Results: The sensitivity and reproducibility of qRT-PCR for the synthetic ssRNA and dsDNA were found to be highly sensitive to VTM with the best results observed for ssRNA in HBSS and PBS-G. Surprisingly, the presence of epithelial cellular material with the ssRNA increased the sensitivity of the qRT-PCR assay. Repeated freeze-thaw cycling decreased the sensitivity of the qRT-PCR with two noted exceptions. : The choice of VTM is critically important to defining the sensitivity of COVID-19 molecular diagnostics assays and this study suggests they can impact upon the stability of the SARS-CoV-2 viral genome. This becomes increasingly important if the virus structure is destabilised before analysis, which can occur due to poor storage conditions. This study suggests that COVID-19 testing performed with glycerol-containing PBS will produce a high level of stability and sensitivity. These results are in agreement with clinical studies reported for patient-derived samples.
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http://dx.doi.org/10.1039/d1nr03933dDOI Listing
September 2021

To centralize or to decentralize? A systematic framework for optimizing rural wastewater treatment planning.

J Environ Manage 2021 Sep 13;300:113673. Epub 2021 Sep 13.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China. Electronic address:

Untreated rural sewage seriously affects the universal access to clean water of rural residents. The lack of decision-support tools in rural sewage treatment (RuST) planning makes it difficult for RuST system to achieve the expected results and is not conducive to the optimal allocation of limited funds. Hence, there is an urgent need to develop a decision-support framework for large-scale RuST planning. For the first time, RuST planning decision-support framework was developed using divide-and-conquer strategy based on rural residents' spatial pattern (RESP) and the optimal pattern of RuST. This framework can be transferred to other countries/regions easily by correcting RESP dataset according to the spatial and environmental characteristics. We confirmed that the variation of RESP made the ideal RuST pattern varied significantly under different topography. And community-based pattern could be the optimal pattern for large-scale RuST planning, when spatial obstacle and RESP were fully considered. The price of onsite sewage treatment facility is the most significant factor for RuST planning. In our selected case, requited onsite facility accounted for 65.51%. For the total investment, the cost of sewer systems accounted for 56.01%, and the average investment in plains, hills, platforms and mountains was 1401, 1803, 1903 and 1859 USD/household, respectively. We expect this research could provide reference for RuST planning in other developing countries/regions all around the world.
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http://dx.doi.org/10.1016/j.jenvman.2021.113673DOI Listing
September 2021

Global insights into lysine acylomes reveal crosstalk between lysine acetylation and succinylation in Streptomyces coelicolor metabolic pathways.

Mol Cell Proteomics 2021 Sep 13:100148. Epub 2021 Sep 13.

CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. Electronic address:

Lysine acylations are reversible and ubiquitous post-translational modifications that play critical roles in regulating multiple cellular processes. In the current study, highly abundant and dynamic acetylation, besides succinylation, was uncovered in a soil bacterium, Streptomyces coelicolor. By affinity enrichment using anti-acetyllysine antibody and the following LC-MS/MS analysis, a total of 1,298 acetylation sites among 601 proteins were identified. Bioinformatics analyses suggested that these acetylated proteins have diverse subcellular localization and were enriched in a wide range of biological functions. Specifically, a majority of the acetylated proteins were also succinylated in the TCA cycle and protein translation pathways, and the bi-modification occurred at the same sites in some proteins. The acetylation and succinylation sites were quantified by knocking out either the deacetylase ScCobB1 or the desuccinylase ScCobB2, demonstrating a possible competitive relationship between the two acylations. Moreover, in-vitro experiments using synthetically modified peptides confirmed the regulatory crosstalk between the two sirtuins, which may be involved in the collaborative regulation of cell physiology. Collectively, these results provided global insights into the S. coelicolor acylomes and laid a foundation for characterizing the regulatory roles of the crosstalk between lysine acetylation and succinylation in the future.
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http://dx.doi.org/10.1016/j.mcpro.2021.100148DOI Listing
September 2021

Small Extracellular Vesicles in the Development, Diagnosis, and Possible Therapeutic Application of Esophageal Squamous Cell Carcinoma.

Front Oncol 2021 30;11:732702. Epub 2021 Aug 30.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Esophageal squamous cell carcinoma (ESCC) persists among the most lethal and broad-spreading malignancies in China. The exosome is a kind of extracellular vesicle (EV) from about 30 to 200 nm in diameter, contributing to the transfer of specific functional molecules, such as metabolites, proteins, lipids, and nucleic acids. The paramount role of exosomes in the formation and development of ESCC, which relies on promoting intercellular communication in the tumor microenvironment (TME), is manifested with immense amounts. Tumor-derived exosomes (TDEs) participate in most hallmarks of ESCC, including tumorigenesis, invasion, angiogenesis, immunologic escape, metastasis, radioresistance, and chemoresistance. Published reports have delineated that exosome-encapsulated cargos like miRNAs may have utility in the diagnosis, as prognostic biomarkers, and in the treatment of ESCC. This review summarizes the function of exosomes in the neoplasia, progression, and metastasis of ESCC, which improves our understanding of the etiology and pathogenesis of ESCC, and presents a promising target for early diagnostics in ESCC. However, recent studies of exosomes in the treatment of ESCC are sparse. Thus, we introduce the advances in exosome-based methods and indicate the possible applications for ESCC therapy in the future.
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http://dx.doi.org/10.3389/fonc.2021.732702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435888PMC
August 2021

Dengzhanxixin Injection Ameliorates Cognitive Impairment Through a Neuroprotective Mechanism Based on Mitochondrial Preservation in Patients With Acute Ischemic Stroke.

Front Pharmacol 2021 30;12:712436. Epub 2021 Aug 30.

State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.

Acute ischemic stroke (AIS) is a global health burden and cognitive impairment is one of its most serious complication. Adequate interventions for AIS may have the potential to improve cognitive outcomes. In the present study, we selected (Vaniot) Hand.-Mazz. injection (Dengzhanxixin injection, DZXI), a widely used Chinese herbal injection, in contrast to edaravone as the positive control drug to test its potential to ameliorates neurological and cognitive impairments caused by AIS. We performed a 2-week randomized trial with these two drugs in AIS patients presenting mild to moderate cognitive impairments. Neuropsychological tests and MRI examinations showed that DZXI attenuated the neurological and cognitive impairments of patients and protected the grey matter in specific regions from ischemic damage. Notably, DZXI exerted better effects than edaravone in some neuropsychological tests, probably due to the protective effect of DZXI on grey matter. To explore the therapeutic mechanisms, we carried out an experiment with a middle cerebral artery occlusion rat model. We found that DZXI decreased the infarct volume and increased the survival of neuronal cells in the ischemic penumbra; furthermore, DZXI modulated the mitochondrial respiratory chain process and preserved the mitochondrial structure in the brain tissue. Overall, our data suggested that the administration of DZXI is effective at ameliorating neurological and cognitive impairments in AIS, and the underlying mechanisms are related to the protective effects of DZXI on cerebral neurons and neuronal mitochondria.
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http://dx.doi.org/10.3389/fphar.2021.712436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435665PMC
August 2021

An engineered IL-2 partial agonist promotes CD8 T cell stemness.

Nature 2021 Sep 15;597(7877):544-548. Epub 2021 Sep 15.

Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Adoptive transfer of antigen-specific T cells represents a major advance in cancer immunotherapy, with robust clinical outcomes in some patients. Both the number of transferred T cells and their differentiation state are critical determinants of effective responses. T cells can be expanded with T cell receptor (TCR)-mediated stimulation and interleukin-2, but this can lead to differentiation into effector T cells and lower therapeutic efficacy, whereas maintenance of a more stem-cell-like state before adoptive transfer is beneficial. Here we show that H9T, an engineered interleukin-2 partial agonist, promotes the expansion of CD8 T cells without driving terminal differentiation. H9T led to altered STAT5 signalling and mediated distinctive downstream transcriptional, epigenetic and metabolic programs. In addition, H9T treatment sustained the expression of T cell transcription factor 1 (TCF-1) and promoted mitochondrial fitness, thereby facilitating the maintenance of a stem-cell-like state. Moreover, TCR-transgenic and chimeric antigen receptor-modified CD8 T cells that were expanded with H9T showed robust anti-tumour activity in vivo in mouse models of melanoma and acute lymphoblastic leukaemia. Thus, engineering cytokine variants with distinctive properties is a promising strategy for creating new molecules with translational potential.
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http://dx.doi.org/10.1038/s41586-021-03861-0DOI Listing
September 2021

Assessment of two-pool multiplex long-amplicon nanopore sequencing of SARS-CoV-2.

J Med Virol 2021 Sep 15. Epub 2021 Sep 15.

Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in COVID-19 pandemic control and elimination efforts, especially by elucidating its global transmission network and illustrating its viral evolution. The deployment of multiplex PCR assays that target SARS-CoV-2 followed by either massively parallel or nanopore sequencing is a widely-used strategy to obtain genome sequences from primary samples. However, multiplex PCR-based sequencing carries an inherent bias of sequencing depth among different amplicons, which may cause uneven coverage. Here we developed a two-pool, long-amplicon 36-plex PCR primer panel with ~1000-bp amplicon lengths for full-genome sequencing of SARS-CoV-2. We validated the panel by assessing nasopharyngeal swab samples with a <30 quantitative reverse transcription PCR cycle threshold value and found that ≥90% of viral genomes could be covered with high sequencing depths (≥20% mean depth). In comparison, the widely-used ARTIC panel yielded 79%-88% high-depth genome regions. We estimated that ~5 Mbp nanopore sequencing data may ensure a >95% viral genome coverage with a ≥10-fold depth and may generate reliable genomes at consensus sequence levels. Nanopore sequencing yielded false-positive variations with frequencies of supporting reads <0.8, and the sequencing errors mostly occurred on the 5' or 3' ends of reads. Thus, nanopore sequencing could not elucidate intra-host viral diversity.
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http://dx.doi.org/10.1002/jmv.27336DOI Listing
September 2021

Treatment of thoracolumbar fractures by temporary posterior instrumentation with selective fusion schemes.

Br J Neurosurg 2021 Sep 15:1-8. Epub 2021 Sep 15.

Department of Orthopedic Surgery, Spine Center, Second Affiliated Hospital of Naval Medical University, Shanghai, P. R. China.

Objective: This retrospective study investigated the clinical and radiographic outcomes following temporary transpedicular posterior instrumentation between two cohorts of patients with thoracolumbar fractures (TLF) who underwent selective or bi-segments intervertebral articular process fusion.

Methods: Patients with TLF who underwent the temporary posterior fixation with selective fusion (Group SF), or bi-segments fusion (Group BF) were studied. Superior intervertebral articular process and interlaminar fusion were performed in Group SF, whereas in Group BF, the patients underwent bi-segments fusion in both superior and inferior articular processes, as well as interlaminar fusion. We measured the distal and proximal intervertebral mobility, regional kyphotic angle, and vertebral height before and after surgery in both groups. Greenough Low-Back Outcome Score was used to assess the clinical outcomes.

Results: Sixty-five patients with TLF from T12 to L2 fractures were enrolled in the study period: 33 patients in the Group SF and 32 patients in the Group BF. All the patients experienced fracture healing (mean follow-up time: 19.7 months). The mean postoperative functional outcomes were 65.0 ± 2.0 points for the Low-Back Outcome Score in the Group SF and 65.2 ± 1.8 for the Group BF. A progressive regional kyphotic angle was observed with time regardless of fusion but was not significantly different between the two groups. There was a statistical difference between unfused inferior proximal adjacent and inferior distal adjacent segment regardless of fracture segments.

Conclusions: The strategy of selective fusion is reported to be useful for the treatment of patients with TLF. The motion in the un-fused and adjacent segment could be better regained after instrumentation removal in the selective fusion group.

Level Of Evidence: Level 3.
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http://dx.doi.org/10.1080/02688697.2021.1976391DOI Listing
September 2021

A novel surgical approach in dealing with the confusing sites in total mesorectal excision: fascial space priority approach with two tunnels established.

Tech Coloproctol 2021 Sep 13. Epub 2021 Sep 13.

Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, 300000, China.

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http://dx.doi.org/10.1007/s10151-021-02512-wDOI Listing
September 2021

Novel recognition mechanism based on oxidative addition of Pt(II) complex-based luminescent probes for hypochlorite ion detection.

Analyst 2021 Sep 13;146(18):5691-5703. Epub 2021 Sep 13.

Institute of Bioengineering, Guangdong Academy of Sciences, Guangzhou 510316, China.

Platinum(II) complexes are the most commonly used anticancer drugs and potential optical materials, but the detectability of Pt(II) complex-based probes is seldom reported. In our previous work, a tetradentate Pt(II) complex Pt-CHO was utilised as a 'turn-off' probe to detect ClO and image cancer cells. However, the recognition mechanism has not been completely clarified and there are still doubts. In this work, three Pt(II) complexes, Pt-H, Pt-CHO and Pt-COOH, were developed to elucidate the mechanism of this class of complexes and refine their property studies. As a result, the UV-visible absorption and luminescence emission experiments, as well as the mass spectrum, proved that the oxidation of Pt(II) to Pt(IV) was the real reason for luminescence quenching, which has nothing to do with aldehyde groups. This first reported mechanism introduces a new type of ClO probe based on Pt(II) complexes, thereby expanding the application fields of platinum complexes. Moreover, the quantum yield measurements, the effect of biomolecules and reversibility were studied to improve the properties of the probes. Theoretical calculations were used to gain an in-depth understanding of optical characteristics and related mechanisms. The cell imaging of RAW264.7 cells under endogenous ClO proved the potential of the probes in bioimaging.
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http://dx.doi.org/10.1039/d1an01048dDOI Listing
September 2021

Noninvasive OCT angiography-based blood attenuation measurements correlate with blood glucose level in the mouse retina.

Biomed Opt Express 2021 Aug 6;12(8):4680-4688. Epub 2021 Jul 6.

State Key Lab of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.

In this study, we investigated the correlation of the blood optical attenuation coefficient (OAC) and the blood glucose concentration (BGC). The blood OAC was measured in mouse retina in vivo by analyzing the depth attenuation of backscattered light under the guidance of OCT angiography (OCTA) vascular mapping, and then its correlation to the BGC was further investigated. The optical attenuation of the blood components presented a more reliable correlation to BGC than that of the background tissues. The arteries and veins presented a blood OAC change of ∼0.05-0.07 mm per 10 mg/dl and a significant (P < 0.001) elevation of blood OAC in diabetic mice was observed. Furthermore, different kinds of vessels also presented different performances. The veins had a higher correlation coefficient (R=0.86) between the measured blood OAC and BGC than that of the arteries (R=0.73). Besides, the blood OAC changes of the specific vessels occur without any obvious change in the vascular morphology in the retina. The blood OAC-BGC correlation suggests a concept of non-invasive OCTA-based glucometry, allowing a fast assessment of the blood glucose of specific vessels with superior motion immunity. A direct glucometry of the retina would be helpful for accurately monitoring the progression of diabetic retinopathy.
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http://dx.doi.org/10.1364/BOE.430104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407843PMC
August 2021

Genetic and immune characteristics of multiple primary lung cancers and lung metastases.

Thorac Cancer 2021 Sep 12. Epub 2021 Sep 12.

Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Background: To explore the genetic and immunophenotyping heterogeneities between patients with intrapulmonary metastasis (IPM) or multiple primary lung cancer (MPLC).

Methods: Whole exome sequencing (WES) and transcriptome sequencing (RNA-seq) were performed on the tissue and blood samples of IPM and MPLC patients to comprehensively analyze the clonal evolution, molecular typing and immunophenotyping.

Results: There was no significant difference in genetic mutation, tumor mutational burden (TMB) value and mutant allele tumor heterogeneity (MATH) value between IPM and MPLC patients. Notably, the loss of heterozygosity (LOH) of human leukocyte antigen (HLA) appeared in all IPM patients, while there was also no significant difference between the two groups. In addition, expression of immune checkpoint-related genes including CTLA-4, BTLA, TIGIT and HAVCR2 in the MPLC group was significantly higher than those in IPM group. At the same time, 86 differentially expressed genes (DEGs) were observed between IPM and MPLC patients with transcriptome sequencing, of which 56 DEGs were upregulated and 30 were downregulated in the IPM group compared with the MPLC group. The cluster analysis revealed that the 86 DEGs could be distinguished in IPM and MPLC samples. Moreover, only the infiltration levels of CD56dim natural killer cells in the IPM group was significantly higher than that in the MPLC group, and the infiltration levels of the remaining 27 immune cell subsets were similar in both groups.

Conclusions: IPM and MPLC are roughly similar in genetic and immune characteristics indicating that genomics alone may not be able to effectively distinguish between IPM and MPLC, which still needs to be comprehensively evaluated with clinical manifestations, imaging, and pathological characteristics.
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http://dx.doi.org/10.1111/1759-7714.14134DOI Listing
September 2021

Conjugated Polymers: Optical Toolbox for Bioimaging and Cancer Therapy.

Small 2021 Sep 12:e2103127. Epub 2021 Sep 12.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu, 215123, P. R. China.

Conjugated polymers (CPs) are capable of coordinating the electron coupling phenomenon to bestow powerful optoelectronic features. The light-harvesting and light-amplifying properties of CPs are extensively used in figuring out the biomedical issues with special emphasis on accurate diagnosis, effective treatment, and precise theranostics. This review summarizes the recent progress of CP materials in bioimaging, cancer therapeutics, and introduces the design strategies by rationally tuning the optical properties. The recent advances of CPs in bioimaging applications are first summarized and the challenges to clear the future directions of CPs in the respective area are discussed. In the following sections, the focus is on the burgeoning applications of CPs in phototherapy of the tumor, and illustrates the underlying photo-transforming mechanism for further molecular designing. Besides, the recent progress in the CPs-assistant drug therapy, mainly including drug delivery, gene therapeutic, the optical-activated reversion of tumor resistance, and synergistic therapy has also been discussed elaborately. In the end, the potential challenges and future developments of CPs on cancer diagnosis and therapy are also illuminated for the improvement of optical functionalization and the promotion of clinical translation.
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http://dx.doi.org/10.1002/smll.202103127DOI Listing
September 2021

Sensitive, High-Speed, and Broadband Perovskite Photodetectors with Built-In TiO Metalenses.

Small 2021 Sep 12:e2102694. Epub 2021 Sep 12.

Laboratory for Advanced Interfacial Materials and Devices, Research Centre for Smart Wearable Technology, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong SAR, China.

Monolithic integration of nanostructured metalenses with broadband light transmission and good charge transport can simultaneously enhance the sensitivity, speed, and efficiency of photodetectors. The realization of built-in broadband metalenses in perovskite photodetectors, however, has been largely challenged by the limited choice of materials and the difficulty in nanofabrication. Here a new type of broadband-transmitting built-in TiO metalens (meta-TiO ) is devised, which is readily fabricated by one-step and lithograph-free glancing angle deposition. The meta-TiO , which comprises of sub-100 nm TiO nanopillars randomly spaced with a wide range of sub-wavelength distances in 5-200 nm, shows high transmittance of light in the wavelength range of 400-800 nm. The meta-TiO also serves as an efficient electron transporting layer to prevent the exciton recombination and facilitate the photoinduced electron extraction and transport. Replacing the conventional mesoporous TiO with the meta-TiO comprehensively leads to enhancing the detection speed by three orders of magnitude to a few hundred nanoseconds, improving the responsivity and detectivity by one order of magnitude to 0.5 A W and 10 Jones, respectively, and extending the linear dynamic range by 50% to 120 dB.
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http://dx.doi.org/10.1002/smll.202102694DOI Listing
September 2021

A gel-like condensation of Cidec generates lipid-permeable plates for lipid droplet fusion.

Dev Cell 2021 Sep 7. Epub 2021 Sep 7.

State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Shanghai Qi Zhi Institute, Shanghai 200030, China. Electronic address:

Membrane contact between intracellular organelles is important in mediating organelle communication. However, the assembly of molecular machinery at membrane contact site and its internal organization correlating with its functional activity remain unclear. Here, we demonstrate that a gel-like condensation of Cidec, a crucial protein for obesity development by facilitating lipid droplet (LD) fusion, occurs at the LD-LD contact site (LDCS) through phase separation. The homomeric interaction between the multivalent N terminus of Cidec is sufficient to promote its phase separation both in vivo and in vitro. Interestingly, Cidec condensation at LDCSs generates highly plastic and lipid-permeable fusion plates that are geometrically constrained by donor LDs. In addition, Cidec condensates are distributed unevenly in the fusion plate generating stochastic sub-compartments that may represent unique lipid passageways during LD fusion. We have thus uncovered the organization and functional significance of geometry-constrained Cidec phase separation in mediating LD fusion and lipid homeostasis.
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http://dx.doi.org/10.1016/j.devcel.2021.08.015DOI Listing
September 2021

Comparative outcomes of endoscopic ultrasound-guided lumen-apposing mental stents drainage for pancreatic pseudocysts and walled-off necrosis: Case series and meta-analysis.

Chronic Dis Transl Med 2021 Sep 11;7(3):157-168. Epub 2021 Aug 11.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing 100050, China.

Background: Endoscopic ultrasound (EUS)-guided transmural drainage for pancreatic fluid collections (PFCs) has become the first-line treatment with quicker recovery and more minor injury compared with surgery and percutaneous drainage. The efficacy of stents implantation and drainage for different PFCs remains controversial, especially lumen-apposing metal stents (LAMS). This study aimed to compare the efficacy and safety of LAMS drainage for pancreatic pseudocysts (PPC) and walled-off necrosis (WON).

Methods: A meta-analysis was performed for LAMS drainage for WON and PPC by systematically searching PubMed, Cochrane, and Embase databases from January 2010 to January 2020. From 2017 to 2019, 12 patients who were treated with LAMS drainage for PFCs in our medical center were also reviewed and included in this study.

Results: Combining 11 copies of documents with the data from our medical center, a total of 585 patients with PFCs were enrolled in this meta-analysis, including 343 patients with WON and 242 with PPC. The technical success rate in WON is not significantly different from that of PPC ( = 0.08 > 0.05). The clinical success of LAMS placement was achieved in 99% vs 89% in PPC and WON, respectively (RR = 0.92, 95% CI: 0.86-0.98,  = 0.01 < 0.05). The further intervention of direct endoscopic necrosectomy was required by 60% of patients in WON group. There was no significant difference in the incidence of adverse events, including infection, bleeding, stent migration and stent occlusion, after LAMS placement between WON and PPC.

Conclusions: Endoscopic ultrasound-guided LAMS for PFCs are feasible, effective with preferable technical and clinical success rates. The clinical effect of LAMS on PPC is slightly better than that of WON, but its adverse reactions still need to be verified in a large-sample prospective study.
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http://dx.doi.org/10.1016/j.cdtm.2021.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413123PMC
September 2021

Knockdown of LINC00657 inhibits the viability, migration and invasion of pancreatic cancer cells by regulating the miR-520h/CKS1B axis.

Exp Ther Med 2021 Oct 9;22(4):1142. Epub 2021 Aug 9.

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Beihua University, Jilin, Jilin 132011, P.R. China.

Long non-coding RNA LINC00657 has a critical role in multiple cancers. The aim of the present study was to investigate the regulatory effect of LINC00657 in pancreatic cancer (PC) and reveal its molecular mechanism of function. The expression levels of LINC00657 and microRNA (miR)-520h were detected by reverse transcription-quantitative PCR in PC tissues and cell lines. MTT, wound healing and Transwell assays were used to detect cell viability, migration and invasion, respectively. Dual-luciferase reporter assay was utilized to examine the relationship between LINC00657 and miR-520h and that between miR-520h and cyclin-dependent kinases regulatory subunit 1 (CKS1B). Western blotting was performed to detect CKS1B expression. The expression levels of LINC00657 and CKS1B were enhanced and miR-520h expression level was reduced in PC tissues and cell lines compared with adjacent normal tissues or HPDE6 cells. LINC00657 knockdown decreased the viability, migration and invasion of PC cells. Additionally, LINC00657 targeted miR-520h and negatively modulated miR-520h expression. Furthermore, miR-520h overexpression inhibited the viability, migration and invasion of PC cells. In addition, miR-520h targeted CKS1B and reversely regulated CKS1B expression. miR-520h inhibition and CKS1B overexpression alleviated the inhibition effect of LINC00657 knockdown on the viability, migration and invasion of PACA-2 PC cells. In conclusion, the results of the present study demonstrated that LINC00657 knockdown repressed the viability, migration and invasion of PC cells via targeting the miR-520h/CKS1B axis, which may offer a future target for PC therapy.
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http://dx.doi.org/10.3892/etm.2021.10576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393733PMC
October 2021

Genetic Architecture and Genome-Wide Adaptive Signatures Underlying Stem Lenticel Traits in .

Int J Mol Sci 2021 Aug 26;22(17). Epub 2021 Aug 26.

National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, No. 35, Qinghua East Road, Beijing 100083, China.

The stem lenticel is a highly specialized tissue of woody plants that has evolved to balance stem water retention and gas exchange as an adaptation to local environments. In this study, we applied genome-wide association studies and selective sweeping analysis to characterize the genetic architecture and genome-wide adaptive signatures underlying stem lenticel traits among 303 unrelated accessions of , which has significant phenotypic and genetic variations according to climate region across its natural distribution. In total, we detected 108 significant single-nucleotide polymorphisms, annotated to 88 candidate genes for lenticel, of which 9 causative genes showed significantly different selection signatures among climate regions. Furthermore, and showed significant association signals and abiotic stress response, so we overexpressed these two genes in and found that the number of stem cells in all three overexpression lines was significantly reduced by overexpression but slightly increased by overexpression, suggesting that both genes are involved in cell division and expansion during lenticel formation. The findings of this study demonstrate the successful application of an integrated strategy for dissecting the genetic basis and landscape genetics of complex adaptive traits, which will facilitate the molecular design of tree ideotypes that may adapt to future climate and environmental changes.
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http://dx.doi.org/10.3390/ijms22179249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431110PMC
August 2021

Construction of a novel predictive nomogram for difficult procedure of endoscopic submucosal dissection for colorectal neoplasms.

Scand J Gastroenterol 2021 Sep 9:1-7. Epub 2021 Sep 9.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Objectives: To determine the predictors of difficult colorectal endoscopic submucosal dissection (ESD) and to develop a preoperative predictive model for difficult colorectal ESD procedures.

Methods: Colorectal neoplasms intended to be resected by ESD in our center between August 2013 and February 2019 were retrospectively enrolled. An ESD procedure which took more than 30 min, failed to remove the lesions en bloc or converted to surgery was defined as difficulty. Logistic regression analysis was conducted to find out the predictors of difficult ESD. A nomogram integrating independent predictors was developed and validated with respect to its discrimination, calibration and clinical application, using the receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA), respectively.

Results: A total of 368 colorectal neoplasms in 355 patients were included. The independent predictors for difficult colorectal ESD were size ≥2 cm (odds ratio [OR] = 6.102,  < .001), positive non-lifting sign (OR = 6.569,  = .005), lesions located in left colon (OR = 2.475,  = .036) or rectum (OR = 2.183,  = .048), laterally spreading tumors (LSTs) (OR = 2.501,  = .008) and less colorectal ESD experience (≤20 cases) (OR = 2.3091,  = .028). The nomogram model incorporating the above predictors performed well in both of the training and validation sets (area under the cure [AUC] = 0.786 and 0.784, respectively). DCA demonstrated the clinical benefit of the nomogram was superior to that of each independent predictor alone.

Conclusions: The nomogram incorporating tumor size, location, morphology, non-lifting sign and ESD experience of operator can be conveniently used to facilitate the preoperative prediction of difficult colorectal ESD.
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http://dx.doi.org/10.1080/00365521.2021.1973089DOI Listing
September 2021

Inferring Gene Regulatory Networks Using the Improved Markov Blanket Discovery Algorithm.

Interdiscip Sci 2021 Sep 8. Epub 2021 Sep 8.

School of Computer Science, Xiangtan University, Xiangtan, 411105, China.

Inferring gene regulatory networks (GRNs) from microarray data can help us understand the mechanisms of life and eventually develop effective therapies. Currently, many computational methods have been used in inferring GRNs. However, owing to high-dimensional data and small samples, these methods often tend to introduce redundant regulatory relationships. Therefore, a novel network inference method based on the improved Markov blanket discovery algorithm, IMBDANET, is proposed to infer GRNs. Specifically, for each target gene, data processing inequality was applied to the Markov blanket discovery algorithm for the accurate differentiation of direct regulatory genes from indirect regulatory genes. Finally, direct regulatory genes were used in constructing GRNs, and the network structure was optimized according to the importance degree score. Experimental results on six public network datasets show that the proposed method can be effectively used to infer GRNs.
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http://dx.doi.org/10.1007/s12539-021-00478-9DOI Listing
September 2021

Identifying the Phenotypic and Temporal Heterogeneity of Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

Front Public Health 2021 19;9:726140. Epub 2021 Aug 19.

School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, United States.

Previous studies discussing phenotypic and temporal heterogeneity of knee osteoarthritis (KOA) separately have fatal limitations that either clustering patients with similar severity or assuming all knees have a single common progression pattern, which are unreliable. This study tried to uncover more reliable information on phenotypic and temporal heterogeneity of KOA. Data were from Osteoarthritis Initiative database. Six hundred and seventy-eight unilateral knees that have greater Kellgren and Lawrence (KL) grade than the contralateral knees at baseline and in all follow-up 48 months were included. Measurements of biomarkers at baseline were chosen. Subtype and Stage Inference model (SuStaIn) was applied as a subtype-progression model to identify subtypes, subtype biomarker progress sequences and stages of KOA. This study identified three subtypes which account for 15, 61, and 24% of knees, respectively. Each subtype has distinct subtype biomarker progress sequence. For knees with KL grade 0/1, 2, 3, and 4, they have different distributions on stage and 26, 53, 89, and 95% of them are strongly assigned to subtypes. When assessing whether a knee has KL (grade ≥ 2), subtypes and stages from subtypes-progression model (SuStaIn) are significantly better fitting than those from subtypes-only (mixture of Gaussians) (likelihood ratio = 105.59, = 2.2 × 10) or stages-only (SuStaIn where setting = 1) (likelihood ratio = 58.04, = 2.57 × 10) model. Stages in subtypes-progression model has greater β than stages-only model. Subtypes from subtypes-progression model have no statistical significance. For subtypes-progression model, stages contain more complete temporal information and subtypes are closer to real OA subtypes.
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http://dx.doi.org/10.3389/fpubh.2021.726140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416902PMC
August 2021
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