Publications by authors named "Kai Huang"

930 Publications

Analyzing mRNAsi-Related Genes Identifies Novel Prognostic Markers and Potential Drug Combination for Patients with Basal Breast Cancer.

Dis Markers 2021 4;2021:4731349. Epub 2021 Oct 4.

The Second Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300600, China.

Basal breast cancer subtype is the worst prognosis subtypes among all breast cancer subtypes. Recently, a new tumor stemness index-mRNAsi is found to be able to measure the degree of oncogenic differentiation of tissues. The mRNAsi involved in a variety of cancer processes is derived from the innovative application of one-class logistic regression (OCLR) machine learning algorithm to the whole genome expression of various stem cells and tumor cells. However, it is largely unknown about mRNAsi in basal breast cancer. Here, we find that basal breast cancer carries the highest mRNAsi among all four subtypes of breast cancer, especially 385 mRNAsi-related genes are positively related to the high mRNAsi value in basal breast cancer. This high mRNAsi is also closely related to active cell cycle, DNA replication, and metabolic reprogramming in basal breast cancer. Intriguingly, in the 385 genes, , , , and can act as independent protective prognostic factors, but and can serve as independent bad prognostic factors in patients with basal breast cancer. Remarkably, we establish a robust prognostic model containing the 6 mRNAsi-related genes that can effectively predict the survival rate of patients with the basal breast cancer subtype. Finally, the drug sensitivity analysis reveals that some drug combinations may be effectively against basal breast cancer via targeting the mRNAsi-related genes. Taken together, our study not only identifies novel prognostic biomarkers for basal breast cancers but also provides the drug sensitivity data by establishing an mRNAsi-related prognostic model.
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http://dx.doi.org/10.1155/2021/4731349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505092PMC
October 2021

A Vimentin-Targeting Oral Compound with Host-Directed Antiviral and Anti-Inflammatory Actions Addresses Multiple Features of COVID-19 and Related Diseases.

mBio 2021 Oct 12:e0254221. Epub 2021 Oct 12.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Su Genomic Resource Center, Medical School of Soochow University, Suzhou, Jiangsu, China.

Damage in COVID-19 results from both the SARS-CoV-2 virus and its triggered overactive host immune responses. Therapeutic agents that focus solely on reducing viral load or hyperinflammation fail to provide satisfying outcomes in all cases. Although viral and cellular factors have been extensively profiled to identify potential anti-COVID-19 targets, new drugs with significant efficacy remain to be developed. Here, we report the potent preclinical efficacy of ALD-R491, a vimentin-targeting small molecule compound, in treating COVID-19 through its host-directed antiviral and anti-inflammatory actions. We found that by altering the physical properties of vimentin filaments, ALD-491 affected general cellular processes as well as specific cellular functions relevant to SARS-CoV-2 infection. Specifically, ALD-R491 reduced endocytosis, endosomal trafficking, and exosomal release, thus impeding the entry and egress of the virus; increased the microcidal capacity of macrophages, thus facilitating the pathogen clearance; and enhanced the activity of regulatory T cells, therefore suppressing the overactive immune responses. In cultured cells, ALD-R491 potently inhibited the SARS-CoV-2 spike protein and human ACE2-mediated pseudoviral infection. In aged mice with ongoing, productive SARS-CoV-2 infection, ALD-R491 reduced disease symptoms as well as lung damage. In rats, ALD-R491 also reduced bleomycin-induced lung injury and fibrosis. Our results indicate a unique mechanism and significant therapeutic potential for ALD-R491 against COVID-19. We anticipate that ALD-R491, an oral, fast-acting, and non-cytotoxic agent targeting the cellular protein with multipart actions, will be convenient, safe, and broadly effective, regardless of viral mutations, for patients with early- or late-stage disease, post-COVID-19 complications, and other related diseases. With the Delta variant currently fueling a resurgence of new infections in the fully vaccinated population, developing an effective therapeutic drug is especially critical and urgent in fighting COVID-19. In contrast to the many efforts to repurpose existing drugs or address only one aspect of COVID-19, we are developing a novel agent with first-in-class mechanisms of action that address both the viral infection and the overactive immune system in the pathogenesis of the disease. Unlike virus-directed therapeutics that may lose efficacy due to viral mutations, and immunosuppressants that require ideal timing to be effective, this agent, with its unique host-directed antiviral and anti-inflammatory actions, can work against all variants of the virus, be effective during all stages of the disease, and even resolve post-disease damage and complications. Further development of the compound will provide an important tool in the fight against COVID-19 and its complications, as well as future outbreaks of new viruses.
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http://dx.doi.org/10.1128/mBio.02542-21DOI Listing
October 2021

Kidney damage causally affects the brain cortical structure: A Mendelian randomization study.

EBioMedicine 2021 Oct 4;72:103592. Epub 2021 Oct 4.

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, PR China. Electronic address:

Background: Alterations in the brain cortical structures of patients with chronic kidney disease (CKD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of kidney damage on brain cortical structure.

Methods: Genome-wide association studies summary data of estimated glomerular filtration rate (eGFR) in 480,698 participants from the CKDGen Consortium were used to identify genetically predicted eGFR. Data from 567,460 individuals from the CKDGen Consortium were used to assess genetically determined CKD; 302,687 participants from the UK Biobank were used to evaluate genetically predicted albuminuria. Further, data from 51,665 patients from the ENIGMA Consortium were used to assess the relationship between genetic predisposition and reduced eGFR, CKD, and progressive albuminuria with alterations in cortical thickness (TH) or surficial area (SA) of the brain. Magnetic resonance imaging was used to measure the SA and TH globally and in 34 functional regions. Inverse-variance weighted was used as the primary estimate whereas MR Pleiotropy RESidual Sum and Outlier, MR-Egger and weighted median were used to detect heterogeneity and pleiotropy.

Findings: At the global level, albuminuria decreased TH (β = -0.07 mm, 95% CI: -0.12 mm to -0.02 mm, P = 0.004); at the functional level, albuminuria reduced TH of pars opercularis gyrus without global weighted (β = -0.11 mm, 95% CI: -0.16 mm to -0.07 mm, P = 3.74×10). No pleiotropy was detected.

Interpretation: Kidney damage causally influences the cortex structure which suggests the existence of a kidney-brain axis.

Funding: This study was supported by the Science and Technology Planning Project of Guangdong Province (Grant No. 2020A1515111119 and 2017B020227007), the National Key Research and Development Program of China (Grant No. 2018YFA0902803), the National Natural Science Foundation of China (Grant No. 81825016, 81961128027, 81772719, 81772728), the Key Areas Research and Development Program of Guangdong (Grant No. 2018B010109006), Guangdong Special Support Program (2017TX04R246), Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, and Grants from the Guangdong Science and Technology Department (2020B1212060018).
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http://dx.doi.org/10.1016/j.ebiom.2021.103592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498227PMC
October 2021

Early 2 factor (E2F) transcription factors contribute to malignant progression and have clinical prognostic value in lower-grade glioma.

Bioengineered 2021 Dec;12(1):7765-7779

Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.

Early 2 factor (E2F) genes encoding a family of transcription factors are significantly associated with apoptosis, metabolism, and angiogenesis in several tumor types. However, the biological functions of E2F transcription factors (E2Fs) and their potential involvement in the malignancy of lower-grade glioma (LGG) remain unclear. We explored the effects of the expression of eight E2F family members on the clinical characteristics of LGG based on the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and GSE16011 datasets. Two LGG subgroups were identified according to the consensus clustering of the eight E2Fs. We employed the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm for further functional experiments and the development of a potential risk score. Two categories of patients with LGG were identified based on the median risk scores. We then developed a nomogram based on the results of the multivariate analysis. Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to validate the bioinformatics results. Our results indicated that E2F family members were significantly involved in the malignancy of LGG and might serve as effective prognostic biomarkers of the disease.
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http://dx.doi.org/10.1080/21655979.2021.1985340DOI Listing
December 2021

Differentiation Ability of Tendon-Derived Stem Cells and Histological Characteristics of Rotator Cuff Remnant on the Greater Tuberosity Degenerated with Age and Chronicity.

Arthroscopy 2021 Oct 1. Epub 2021 Oct 1.

Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address:

Purpose: To explore and measure the presence and activity of tendon-derived stem cells (TDSCs), as well as histological changes of rotator cuff remnant by age and chronicity of the rotator cuff tear (RCT).

Methods: 154 patients with a full-thickness tear of supraspinatus and/or infraspinatus tendon were included. 52 qualified remnants of the greater tuberosity were captured through arthroscopy. TDSCs in the remnants were isolated for proliferation ability, basal gene expression, and trilineage differentiation detection. Histological characteristics were evaluated by observation of staining under a light microscope and transmission electron microscopy (TEM). To observe the effect of age, samples were divided into two groups: young (<60 years old) and old (≥60 years old). For chronicity comparison, samples were divided into three groups: acute group (<3 months), intermediate group (3-12 months), and chronic group (≥12 months).

Results: Between age groups, the remnants in older patients were found to have lower TDSC proliferation ability (cell counting kit-8 results, old: .5325 ± .050, young: .6623 ± .196; P = .008) and basal expression of aggrecan (.630 ± .239; P = .002) and TGF-β1 (transforming growth factor-β1, .589 ± .326, P = .008), weaker ability of chondrogenic differentiation. Furthermore, the remnant tendons in chronic group was found to have weaker adipogenic and chondrogenic differentiation ability of TDSCs, lower tendon degenerative score (acute: 3.57 ± 1.902, intermediate: 5.94 ± 2.313, chronic: 6.86 ± 2.193; P = .023), increased type III collagen region ratio in insertion area (acute: 86.10% ± 8.29%, intermediate: 94.06% ± 5.36%, chronic: 98.90% ± .49%; P = .023), and larger fibril diameters.

Conclusion: Differentiation ability of TDSCs derived from the rotator cuff remnant was reduced with age and chronicity. Histological degeneration of remnant tendon deteriorated with chronicity. Remnant in the greater tuberosity was still alive, but those in young or acute injury patients were more active after full-thickness RCT.

Clinical Relevance: TDSCs exist in rotator cuff remnant on the greater tuberosity and have multilineage differentiation ability. But the remnant degenerated with age and chronicity.
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http://dx.doi.org/10.1016/j.arthro.2021.09.027DOI Listing
October 2021

Novel porous starch/alginate hydrogels for controlled insulin release with dual response to pH and amylase.

Food Funct 2021 Oct 4;12(19):9165-9177. Epub 2021 Oct 4.

School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.

An important principle in the development of oral insulin is to protect insulin from the harsh conditions of the stomach and release it in a controlled manner in the intestine. In the present study, novel insulin-loaded porous starch-alginate hydrogel systems (In-S-Alg) including In-MS-Alg (prepared with porous maize starch), In-WS-Alg (porous waxy maize starch), and In-RS-Alg (porous rice starch) were successfully developed. As a representative, In-MS-Alg was further coated with gelatinized-retrograded high amylose maize starch (HA) films with different thicknesses to prepare In-MS-HA/Alg hydrogel beads for improving the functionality of controlled release of insulin under the action of α-amylase. The In-S-Alg and In-MS-HA/Alg hydrogel beads were evaluated in terms of structural and morphological properties, encapsulation effect on insulin as well as its release behavior. The results show that insulin was distributed in the pores and cavities of porous starch granules. In In-MS-HA/Alg hydrogel beads, insulin was increasingly blocked inside porous starch with the increased thickness of the HA film. Encapsulation efficiency of insulin in all In-S-Alg and In-MS-HA/Alg hydrogel beads was >80%. Amazingly, both the hydrogel beads successfully achieved the goal of triggered release upon pH changes and α-amylase addition. Most of the insulin (about 90%) was retained in the simulated gastric fluid; while the release rate of insulin in the simulated intestinal fluid increased gradually, and was further accelerated in the presence of α-amylase. Furthermore, for the In-MS-HA/Alg hydrogel beads, the insulin release rate can be gradually reduced by increasing the thickness of the HA film, which provided the possibility to match the rate of increase of the blood glucose level after the intake of food with different glycemic indices. Therefore, the novel hydrogel prepared in this study may be a promising and safe delivery carrier for oral insulin.
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http://dx.doi.org/10.1039/d1fo01411kDOI Listing
October 2021

Achieving stable Na metal cycling via polydopamine/multilayer graphene coating of a polypropylene separator.

Nat Commun 2021 Oct 1;12(1):5786. Epub 2021 Oct 1.

State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, 116023, Dalian, China.

Sodium metal batteries are considered one of the most promising low-cost high-energy-density electrochemical energy storage systems. However, the growth of unfavourable Na metal deposition and the limited cell cycle life hamper the application of this battery system at a large scale. Here, we propose the use of polypropylene separator coated with a composite material comprising polydopamine and multilayer graphene to tackle these issues. The oxygen- and nitrogen- containing moieties as well as the nano- and meso- porous network of the coating allow cycling of Na metal electrodes in symmetric cell configuration for over 2000 h with a stable 4 mV overpotential at 1 mA cm. When tested in full Na || NaV(PO) coin cell, the coated separator enables the delivery of a stable capacity of about 100 mAh g for 500 cycles (90% capacity retention) at a specific current of 235 mA g and satisfactory rate capability performances (i.e., 75 mAh g at 3.5 A g).
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http://dx.doi.org/10.1038/s41467-021-26032-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486844PMC
October 2021

Human Mitochondrial Ribosomal RNA Modification-Based Classification Contributes to Discriminate the Prognosis and Immunotherapy Response of Glioma Patients.

Front Immunol 2021 9;12:722479. Epub 2021 Sep 9.

Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Background: Epigenetic regulations of the tumor microenvironment (TME) and immunotherapy have been investigated in recent years. Nevertheless, the potential value of mitochondrial ribosomal RNA (mt-rRNA) modification in regulation of the TME and immunotherapy remains unknown.

Methods: We comprehensively investigated the mt-rRNA-modification patterns in glioma patients based on nine regulators of mt-rRNA. Subsequently, these modification patterns were correlated systematically with immunologic characteristics and immunotherapy. An "mt-rRNA predictor" was constructed and validated in multiple publicly available cohorts to provide guidance for prognosis prediction and immunotherapy of glioma patients.

Results: Two distinct patterns of mt-rRNA modification were determined based on the evidence that nine regulators of mt-rRNA correlated significantly with most clinicopathologic characteristics, immunomodulators, TME, immune-checkpoint blockers (ICBs), and prognosis. Patients with mt-rRNA subtype II presented significantly poorer overall survival/progression-free survival (OS/PFS), but higher tumor mutational burden (TMB), more somatic mutations, and copy number variation (CNV). These two mt-rRNA subtypes had distinct TME patterns and responses to ICB therapy. An mt-rRNA predictor was constructed and validated in four glioma cohorts. The subtype with high mt-rRNA score, characterized by increased TMB, infiltration of immune cells, and activation of immunity, suggested an immune-activated phenotype, and was also linked to greater sensitivity to immunotherapy using anti-programmed cell death protein 1 (PD-1) but resistance to temozolomide.

Conclusions: Regulators of mt-rRNA modification have indispensable roles in the complexity and diversity of the TME and prognosis. This novel classification based on patterns of mt-rRNA modification could provide an effective prognostic predictor and guide more appropriate immunotherapy/chemotherapy strategies for glioma patients.
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http://dx.doi.org/10.3389/fimmu.2021.722479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458820PMC
September 2021

Association between anion gap and mortality of aortic aneurysm in intensive care unit after open surgery.

BMC Cardiovasc Disord 2021 Sep 23;21(1):458. Epub 2021 Sep 23.

Department of Cardiovascular Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 33, Yingfeng Road, Haizhu District, Guangzhou, 510000, Guangdong Province, China.

Background: There has not been a well-accepted prognostic model to predict the mortality of aortic aneurysm patients in intensive care unit after open surgery repair. Otherwise, our previous study found that anion gap was a prognosis factor for aortic aneurysm patients. Therefore, we wanted to investigate the relationship between anion gap and mortality of aortic aneurysm patients in intensive care unit after open surgery repair.

Methods: From Medical Information Mart for Intensive Care III, data of aortic aneurysm patients in intensive care unit after open surgery were enrolled. The primary clinical outcome was defined as death in intensive care unit. Univariate analysis was conducted to compare the baseline data in different groups stratified by clinical outcome or by anion gap level. Restricted cubic spline was drawn to find out the association between anion gap level and mortality. Subgroup analysis was then conducted to show the association in different level and was presented as frost plot. Multivariate regression models were built based on anion gap and were adjusted by admission information, severity score, complication, operation and laboratory indicators. Receiver operating characteristic curves were drawn to compare the prognosis ability of anion gap and simplified acute physiology score II. Decision curve analysis was finally conducted to indicate the net benefit of the models.

Results: A total of 405 aortic aneurysm patients were enrolled in this study and the in-intensive-care-unit (in-ICU) mortality was 6.9%. Univariate analysis showed that elevated anion gap was associated with high mortality (P value < 0.001), and restricted cubic spline analysis showed the positive correlation between anion gap and mortality. Receiver operating characteristic curve showed that the mortality predictive ability of anion gap approached that of simplified acute physiology score II and even performed better in predicting in-hospital mortality (P value < 0.05). Moreover, models based on anion gap showed that 1 mEq/L increase of anion gap improved up to 42.3% (95% confidence interval 28.5-59.8%) risk of death.

Conclusions: The level of serum anion gap was an important prognosis factor for aortic aneurysm mortality in intensive care unit after open surgery.
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http://dx.doi.org/10.1186/s12872-021-02263-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459533PMC
September 2021

Isoliquiritigenin alleviates LPS/ D-GalN-induced acute liver failure by activating the PGC-1α/ Nrf2 pathway to reduce oxidative stress and inflammatory response.

Int Immunopharmacol 2021 Sep 20;100:108159. Epub 2021 Sep 20.

Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address:

Acute liver failure (ALF) is a dramatic liver disease characterized by large areas of inflammation. However, there are no available effective targeted drugs for ALF treatment. In the study, serum biochemical index and H&E were used to explore the amelioration of the liver histopathological changes. The oxidative stress kits, quantitative real-time PCR, western blot, immunohistochemistry, immunofluorescence staining, reactive oxygen species (ROS), and siRNA were used to elucidate the mechanisms underlying isoliquiritigenin (ISL) protection. The results showed that ISL significantly improved the liver pathological changes. Furthermore, ISL reduced oxidative stress by altering the expression of PGC-1α, Nrf2, HO-1, NQO1, Keap1, GCLC, and GCLM in damaged hepatocytes. Moreover, the levels of inflammation-related genes including NLRP3 inflammasome, IL-1β, IL-6, TNF-α, iNOS, and Mip-2 were repressed by ISL. In addition, ISL alleviated LPS/D-GalN-induced hepatocytes apoptosis by increasing the Bcl-2/Bax ratio and suppressing the expression of cleaved caspase-3. Further in vivo and in vitro evidence proved the involvement of the PGC-1α/Nrf2 signaling pathway in ISL protection. In conclusion, ISL improves the ability of anti-oxidative stress, alleviates inflammatory reaction, apoptosis, and inhibits NLRP3 inflammasome to protect lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF through activating the PGC-1α/Nrf2 pathway, which provides the possibility for the treatment of ALF.
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http://dx.doi.org/10.1016/j.intimp.2021.108159DOI Listing
September 2021

Ubiquitination Flow Repressors: Enhancing Wound Healing of Infectious Diabetic Ulcers through Stabilization of Polyubiquitinated Hypoxia-Inducible Factor-1α by Theranostic Nitric Oxide Nanogenerators.

Adv Mater 2021 Sep 23:e2103593. Epub 2021 Sep 23.

Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China.

Current treatments for diabetic ulcers (DUs) remain unsatisfactory due to the risk of bacterial infection and impaired angiogenesis during the healing process. The increased degradation of polyubiquitinated hypoxia-inducible factor-1α (HIF-1α) compromises wound healing efficacy. Therefore, the maintenance of HIF-1α protein stability might help treat DU. Nitric oxide (NO) is an intrinsic biological messenger that functions as a ubiquitination flow repressor and antibacterial agent; however, its clinical application in DU treatment is hindered by the difficulty in controlling NO release. Here, an intelligent near-infrared (NIR)-triggered NO nanogenerator ([email protected]@ssPDA-Cy7/IR786s, abbreviated as [email protected]) is presented. [email protected] represses ubiquitination-mediated proteasomal degradation of HIF-1α by inhibiting its interaction with E3 ubiquitin ligases under NIR irradiation. Increased HIF-1α expression in endothelial cells by [email protected] enhances angiogenesis in wound sites, promoting vascular endothelial growth factor (VEGF) secretion and cell proliferation and migration. [email protected] also enables early detection of wound infections and ROS-mediated killing of bacteria. The potential clinical utility of [email protected] is further demonstrated in infected full-thickness DU model under NIR irradiation. [email protected] is the first reported HIF-1α-stabilizing advanced nanomaterial, and further materials engineering might offer a facile, mechanism-based method for clinical DU management.
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http://dx.doi.org/10.1002/adma.202103593DOI Listing
September 2021

Development of SAB model for predicting mortality in intensive care unit after aortic aneurysm surgery.

Ann Palliat Med 2021 Sep 13. Epub 2021 Sep 13.

Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Aortic aneurysm (AA) patients after vascular surgery are at high risk of death, some of them need intensive care. Our aim was to develop a simplified model with baseline data within 24 hours of intensive care unit (ICU) admission to early predict mortality.

Methods: Univariate analysis and least absolute shrinkage and selection operator were used to select important variables, which were then taken into logistic regression to fit the model. Discrimination and validation were used to evaluate the performance of the model. Bootstrap method was conducted to perform internal validation. Finally, decision clinical analysis curve was used to test the clinical usefulness of the model.

Results: We obtained baseline data of 482 AA patients from Medical Information Mart for Intensive Care III database, 33 (6.8%) of whom died in ICU. Our final model contained three variables and was called SAB model based on initials of three items [Sepsis, Anion gap, Bicarbonate (SAB)]. Area under the curve of SAB was 0.904 (95% CI: 0.841-0.967) while brier score was 0.043 (95% CI: 0.028-0.057). After internal validation, corrected area under the curve was 0.898 and brier score was 0.045, which showed good prediction ability of SAB model. The model can be assessed on https://vascularmodel.shinyapps.io/ AorticAneurysm/.

Conclusions: SAB model derived in this study can be easily used to predict in-ICU mortality of AA patients after surgery precisely.
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http://dx.doi.org/10.21037/apm-21-1660DOI Listing
September 2021

Inhibition of NFAT suppresses foam cell formation and the development of diet-induced atherosclerosis.

FASEB J 2021 10;35(10):e21951

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

Deciphering the molecular and cellular processes involved in foam cell formation is critical for us to understand the pathogenesis of atherosclerosis. Nuclear factor of activated T cells (NFAT) is a transcription factor originally identified as a key player in the differentiation of T cells and maturation of immune system. Nowadays it has been brought into attention that NFAT also regulates multiple pathophysiological processes and targeted intervention in NFAT may be effective in the treatment of some cardiovascular diseases. However, whether NFAT is involved in foam cell formation remains elusive. NFAT in human monocyte-derived macrophage was activated by ox-LDL and translocated from the cytoplasm to the nucleus. NFAT then directly bound to peroxisome proliferator-activated receptor γ (PPARγ) in the nucleus and negatively regulated its transcriptional activity. NFATc2 knockdown or NFAT inhibitor 11R-VIVIT increased cholesterol efflux (by activating PPARγ-LXRα-ABCA1 cascade) and reduced the uptake of modified lipoprotein (in a PPARγ-independent way) in macrophage, thus prevented foam cell formation. Besides, 11R-VIVIT also exerted a protective role in the development of atherosclerosis in western diet-fed ApoE mice. These results suggest NFAT inhibition as a potential therapeutic strategy in atherosclerosis.
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http://dx.doi.org/10.1096/fj.202100947RDOI Listing
October 2021

The Classification of Six Common Skin Diseases Based on Xiangya-Derm: Development of a Chinese Database for Artificial Intelligence.

J Med Internet Res 2021 Sep 21;23(9):e26025. Epub 2021 Sep 21.

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

Background: Skin and subcutaneous disease is the fourth-leading cause of the nonfatal disease burden worldwide and constitutes one of the most common burdens in primary care. However, there is a severe lack of dermatologists, particularly in rural Chinese areas. Furthermore, although artificial intelligence (AI) tools can assist in diagnosing skin disorders from images, the database for the Chinese population is limited.

Objective: This study aims to establish a database for AI based on the Chinese population and presents an initial study on six common skin diseases.

Methods: Each image was captured with either a digital camera or a smartphone, verified by at least three experienced dermatologists and corresponding pathology information, and finally added to the Xiangya-Derm database. Based on this database, we conducted AI-assisted classification research on six common skin diseases and then proposed a network called Xy-SkinNet. Xy-SkinNet applies a two-step strategy to identify skin diseases. First, given an input image, we segmented the regions of the skin lesion. Second, we introduced an information fusion block to combine the output of all segmented regions. We compared the performance with 31 dermatologists of varied experiences.

Results: Xiangya-Derm, as a new database that consists of over 150,000 clinical images of 571 different skin diseases in the Chinese population, is the largest and most diverse dermatological data set of the Chinese population. The AI-based six-category classification achieved a top 3 accuracy of 84.77%, which exceeded the average accuracy of dermatologists (78.15%).

Conclusions: Xiangya-Derm, the largest database for the Chinese population, was created. The classification of six common skin conditions was conducted based on Xiangya-Derm to lay a foundation for product research.
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http://dx.doi.org/10.2196/26025DOI Listing
September 2021

Vancomycin Hydrochloride Loaded Hydroxyapatite Mesoporous Microspheres with Micro/Nano Surface Structure to Increase Osteogenic Differentiation and Antibacterial Ability.

J Biomed Nanotechnol 2021 Aug;17(8):1668-1678

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan 430070, PR China.

As infection induced by the implant will lead to operation failure, the implant material must be endowed with certain antibacterial properties. Hydroxyapatite (HA) mesoporous microspheres have been widely used in bone repair due to their advantages, including simple synthesis, good osteogenic properties and drug loading capacity. In this study, vancomycin hydrochloride-loaded mesoporous hydroxyapatite microspheres with micro/nanosurface structures were synthesized to increase osteogenic differentiation and antibacterial ability. Phytic acid (IP6) was used as a template to prepare mesoporous hydroxyapatite microspheres composed of fibres, flakes and smooth surfaces by the hydrothermal homogeneous precipitation method, and the corresponding specific surface areas were 65.20 m²/g, 75.13 m²/g and 71.27 m²/g, respectively. Vancomycin hydrochloride (Van) was used as the drug model to study the drug loading and release characteristics of the microspheres, as well as the antibacterial properties after treatment. In addition, during cocultivation with MC3T3-E1 preosteoblasts, HA microspheres assembled via flakes exhibited better cell compatibility, which promoted cell proliferation, alkaline phosphatase (ALP) activity, and the formation of calcium nodules and increased the expression of osteogenic differentiation-related proteins such as Runx-2, osteopontin (OPN) and collagen I (COL I). These results indicated that the HA microspheres prepared in this experiment have broad application prospects in drug delivery systems and bone repair.
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http://dx.doi.org/10.1166/jbn.2021.3128DOI Listing
August 2021

Conservation and Identity Selection of Cationic Residues Flanking the Hydrophobic Regions in Intermediate Filament Superfamily.

Front Chem 2021 2;9:752630. Epub 2021 Sep 2.

State Key Laboratory of Medical Molecular Biology, School of Basic Medicine Peking Union Medical College, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Beijing, China.

The interplay between the hydrophobic interactions generated by the nonpolar region and the proximal functional groups within nanometers of the nonpolar region offers a promising strategy to manipulate the intermolecular hydrophobic attractions in an artificial molecule system, but the outcomes of such modulations in the building of a native protein architecture remain unclear. Here we focus on the intermediate filament (IF) coiled-coil superfamily to assess the conservation of positively charged residue identity via a biostatistical approach. By screening the disease-correlated mutations throughout the IF superfamily, 10 distinct hotspots where a cation-to-cation substitution is associated with a pathogenic syndrome have been identified. The analysis of the local chemical context surrounding the hotspots revealed that the cationic diversity depends on their separation distance to the hydrophobic domain. The nearby cationic residues flanking the hydrophobic domain of a helix (separation <1 nm) are relatively conserved in evolution. In contrast, the cationic residues that are not adjacent to the hydrophobic domain (separation >1 nm) tolerate higher levels of variation and replaceability. We attribute this bias in the conservation degree of the cationic residue identity to reflect the interplay between the proximal cations and the hydrophobic interactions.
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http://dx.doi.org/10.3389/fchem.2021.752630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443778PMC
September 2021

Optogenetic Control of Non-Apoptotic Cell Death.

Adv Sci (Weinh) 2021 07 6;8(13):2100424. Epub 2021 May 6.

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Hangzhou Zhejiang 310022 China.

Herein, a set of optogenetic tools (designated LiPOP) that enable photoswitchable necroptosis and pyroptosis in live cells with varying kinetics, is introduced. The LiPOP tools allow reconstruction of the key molecular steps involved in these two non-apoptotic cell death pathways by harnessing the power of light. Further, the use of LiPOPs coupled with upconversion nanoparticles or bioluminescence is demonstrated to achieve wireless optogenetic or chemo-optogenetic killing of cancer cells in multiple mouse tumor models. LiPOPs can trigger necroptotic and pyroptotic cell death in cultured prokaryotic or eukaryotic cells and in living animals, and set the stage for studying the role of non-apoptotic cell death pathways during microbial infection and anti-tumor immunity.
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http://dx.doi.org/10.1002/advs.202100424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438606PMC
July 2021

Minimally invasive transforaminal lumbar interbody fusion versus oblique lateral interbody fusion for lumbar degenerative disease: a meta-analysis.

BMC Musculoskelet Disord 2021 Sep 18;22(1):802. Epub 2021 Sep 18.

Laboratory of Stem Cell and Tissue Engineering, Orthopaedic Research Institute, Department of Orthopaedics, West China Hospital, Sichuan University, Keyuan fourth Road, Gaopeng Avenue, Chengdu, Sichuan, 610041, People's Republic of China.

Background: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and oblique lateral interbody fusion (OLIF) are widely used in the treatment of lumbar degenerative diseases. In the present study, a meta-analysis was conducted to compare the clinical and radiographic efficacy of these two procedures.

Methods: A systematic literature review was performed, and the quality of retrieved studies was evaluated with the Newcastle-Ottawa Scale (NOS). Clinical outcomes, including operation time, intraoperative blood loss, improvement in Visual Analogue Scale (VAS), improvement in Oswestry Disability Index (ODI), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) effectiveness rate and complications, in addition to radiographic outcomes, including restoration of disc height, disc angle, overall lumbar lordosis, fusion rate and subsidence, were extracted and input into a fixed or random effect model to compare the efficacy of MIS-TLIF and OLIF.

Results: Seven qualified studies were included. Clinically, OLIF resulted in less intraoperative blood loss and shorter operation time than MIS-TLIF. Improvement of VAS for leg pain was more obvious in the OLIF group (P < 0.0001), whereas improvement of VAS for back pain (P = 0.08) and ODI (P = 0.98) as well as JOABPEQ effectiveness rate (P = 0.18) were similar in the two groups. Radiographically, OLIF was more effective in restoring disc height (P = 0.01) and equivalent in improving the disc angle (P = 0.18) and lumbar lordosis (P = 0.48) compared with MIS-TLIF. The fusion rate (P = 0.11) was similar in both groups, while the subsidence was more severe in the MIS-TLIF group (P < 0.00001).

Conclusions: The above evidence suggests that OLIF is associated with a shorter operation time (with supplementary fixation in the prone position) and less intraoperative blood loss than MIS-TLIF and can lead to better leg pain alleviation, disc height restoration and subsidence resistance. No differences regarding back pain relief, functional recovery, complications, disc angle restoration, lumbar lordosis restoration and fusion rate were found. However, due to the limited number of studies, our results should be confirmed with high-level studies to fully compare the therapeutic efficacy of MIS-TLIF and OLIF.

Trial Registration: PROSPERO ID:  CRD42020201903 .
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http://dx.doi.org/10.1186/s12891-021-04687-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449429PMC
September 2021

[Effectiveness and safety of tranexamic acid combined with intraoperative controlled hypotension on reducing perioperative blood loss in primary total hip arthroplasty].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Sep;35(9):1133-1140

Department of Orthopedics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China.

Objective: To evaluate the effectiveness and safety of tranexamic acid (TXA) combined with intraoperative controlled hypotension (ICH) for reducing perioperative blood loss in primary total hip arthroplasty (THA).

Methods: The clinical data of 832 patients with initial THA due to osteonecrosis of femoral head between January 2017 and July 2020 were retrospectively analyzed. All patients received TXA treatment, and 439 patients (hypotension group) received ICH treatment with an intraoperative mean arterial pressure (MAP) below 80 mm Hg (1 mm Hg=0.133 kPa) while 393 patients (normotension group) received standard general anesthesia with no special invention on blood pressure. There was no significant difference in age, gender, body mass index, American Society of Anesthesiologists (ASA) classification, basic arterial pressure, hip range of motion, internal diseases, preoperative hemoglobin (HB) and hematocrit (HCT), coagulation function, surgical approach, and TXA dosage between the two groups ( >0.05). The perioperative blood loss and blood transfusion, anesthesia and operation time, hospitalization stay, postoperative range of motion, and complications were recorded and compared between the two groups. The patients were further divided into MAP<70 mm Hg group (group A), MAP 70-80 mm Hg group (group B), and normotension group (group C). The perioperative blood loss and postoperative complications were further analyzed to screen the best range of blood pressure.

Results: The intraoperative MAP, total blood loss, dominant blood loss, recessive blood loss, blood transfusion rate and blood transfusion volume, anesthesia time, operation time, and hospitalizarion stay in the hypotension group were significantly lower than those in the normotension group ( <0.05). The postoperative hip flexion range of motion in the hypotension group was significantly better than that of the normotension group ( =2.743, =0.006), but there was no significant difference in the abduction range of motion between the two groups ( =0.338, =0.735). In terms of postoperative complications, the incidence of postoperative hypotension in the hypotension group was significantly higher than that in the normotension group ( =6.096, =0.014), and there was no significant difference in the incidence of other complications ( >0.05). There was no stroke, pulmonary embolism, or deep vein thrombosis in the two groups, and no patients died during hospitalization. Subgroup analysis showed that there was no significant difference in total blood loss, dominant blood loss, and recessive blood loss in groups A and B during the perioperative period ( >0.05), which were significantly lower than those in group C ( <0.05). There was no significant difference in blood transfusion rate, blood transfusion volume, and incidence of acute myocardial injury between 3 groups ( >0.05); the incidence of acute kidney injury in group A was significantly higher than that in group B, and the incidence of postoperative hypotension in group A was significantly higher than that in groups B and C ( <0.05), but no significant difference was found between groups B and C ( >0.05).

Conclusion: The combination of TXA and ICH has a synergistic effect. Controlling the intraoperative MAP at 70-80 mm Hg can effectively reduce the perioperative blood loss during the initial THA, and it is not accompanied by postoperative complications.
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http://dx.doi.org/10.7507/1002-1892.202103230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444141PMC
September 2021

A Quasi-Experimental Study on the Effectiveness of Compulsory and Voluntary Treatment Settings for 1,299 Drug Abusers in Hunan, China.

Front Psychiatry 2021 27;12:613665. Epub 2021 Aug 27.

Second Xiangya Hospital, Central South University, Changsha, China.

Although the type and structure of substance abuse treatment have changed, the overall approaches of drug rehabilitation in China has remained largely unchanged. Evidence of effectiveness for compulsory drug rehabilitation centers (CRCs) and voluntary drug rehabilitation centers (VRCs) remains mixed. The main objective of our study is to reveal the outcomes of CRCs and VRCs and examine the factors associated with relapse in these two centers. In this cross-sectional study, we recruited a total of 1,299 drug abusers in Hunan Province, 709 from CRCs and 590 from VRC, respectively. We used Pearson chi-squared test and -test to examine the differences in demographics and drug-related characteristics. Binary logic regression was used to examine the relationship between important factors and relapse in CRCs and VRC. Patients from CRCs and VRC significantly differed in age, sex, types of drug used, medical illness, education, occupation, mental illness, and marital status. After drug rehabilitation, both groups both had improved in occupation, family support, and social function ( < 0.05). In addition, employment and family support were significantly associated with a decreased risk of relapse ( < 0.05). This study revealed that compulsory rehabilitation is as effective as voluntary rehabilitation in (1) getting jobs and increasing monthly income, (2) having a good relationship with family, and (3) becoming more satisfied with their spared time. The components of these two settings were very different and may imply the necessity of these two approaches in China. In addition, employment and family support may prevent relapse.
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http://dx.doi.org/10.3389/fpsyt.2021.613665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429503PMC
August 2021

Molecular Ferroelectric-Based Flexible Sensors Exhibiting Supersensitivity and Multimodal Capability for Detection.

Adv Mater 2021 Sep 12:e2104107. Epub 2021 Sep 12.

Department of Materials Science and Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.

Although excellent dielectric, piezoelectric, and pyroelectric properties matched with or even surpassing those of ferroelectric ceramics have been recently discovered in molecular ferroelectrics, their successful applications in devices are scarce. The fracture proneness of molecular ferroelectrics under mechanical loading precludes their applications as flexible sensors in bulk crystalline form. Here, self-powered flexible mechanical sensors prepared from the facile deposition of molecular ferroelectric [C(NH ) ]ClO onto a porous polyurethane (PU) matrix are reported. [C(NH ) ]ClO -PU is capable of detecting pressure of 3 Pa and strain of 1% that are hardly accessible by the state-of-the-art piezoelectric, triboelectric, and piezoresistive sensors, and presents the ability of sensing multimodal mechanical forces including compression, stretching, bending, shearing, and twisting with high cyclic stability. This scaling analysis corroborated with computational modeling provides detailed insights into the electro-mechanical coupling and establishes rules of engineering design and optimization for the hybrid sponges. Demonstrative applications of the [C(NH ) ]ClO -PU array suggest potential uses in interactive electronics and robotic systems.
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http://dx.doi.org/10.1002/adma.202104107DOI Listing
September 2021

Successful management of rhabdomyolysis with acute infection resulting from chronic sacrococcygeal pressure ulcers in a paraplegic patient: a case report.

J Int Med Res 2021 Sep;49(9):3000605211039820

Department of Orthopedics, 414282Tongde Hospital of Zhejiang Province, Tongde Hospital of Zhejiang Province, Hangzhou, China.

Rhabdomyolysis, a potentially life-threatening syndrome, is caused by the breakdown of skeletal muscle cells and leakage of intramyocellular contents into the bloodstream. The treatment of rhabdomyolysis resulting from chronic sacrococcygeal pressure ulcers has been rarely reported. A 62-year-old man developed a high fever and dark-colored urine. For the past 30 years, he had lived with paraplegia, which led to his immobility. Physical examination showed evidence of repeated dehiscence and exudation of the wound on his sacrococcygeal region with loss of skin sensation. Upon corroboration of the physical examination findings and laboratory test results, the patient was diagnosed with rhabdomyolysis with an acute infection resulting from sacrococcygeal pressure ulcers. We first debrided the necrotic tissue and then repaired the chronic ulcer. The wound dressing was changed frequently, and antimicrobial therapy and nutritional support were included in the treatment. The fever and dark-colored urine gradually resolved postoperatively. The patient's renal function also improved according to the typical laboratory indicators, and the size of the pressure ulcers decreased to some extent. The patient was discharged after 1 month of hospitalization. This case highlights that accurate diagnosis is critical for administration of precise treatment to paraplegic patients with progressive rhabdomyolysis.
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http://dx.doi.org/10.1177/03000605211039820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438273PMC
September 2021

Generation and characterization of cardiac valve endothelial-like cells from human pluripotent stem cells.

Commun Biol 2021 09 6;4(1):1039. Epub 2021 Sep 6.

Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

The cardiac valvular endothelial cells (VECs) are an ideal cell source that could be used for making the valve organoids. However, few studies have been focused on the derivation of this important cell type. Here we describe a two-step chemically defined xeno-free method for generating VEC-like cells from human pluripotent stem cells (hPSCs). HPSCs were specified to KDR/ISL1 multipotent cardiac progenitors (CPCs), followed by differentiation into valve endothelial-like cells (VELs) via an intermediate endocardial cushion cell (ECC) type. Mechanistically, administration of TGFb1 and BMP4 may specify VEC fate by activating the NOTCH/WNT signaling pathways and previously unidentified targets such as ATF3 and KLF family of transcription factors. When seeded onto the surface of the de-cellularized porcine aortic valve (DCV) matrix scaffolds, hPSC-derived VELs exhibit superior proliferative and clonogenic potential than the primary VECs and human aortic endothelial cells (HAEC). Our results show that hPSC-derived valvular cells could be efficiently generated from hPSCs, which might be used as seed cells for construction of valve organoids or next generation tissue engineered heart valves.
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http://dx.doi.org/10.1038/s42003-021-02571-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421482PMC
September 2021

Regulation of functional groups on graphene quantum dots directs selective CO to CH conversion.

Nat Commun 2021 Sep 6;12(1):5265. Epub 2021 Sep 6.

Department of Chemical and Environmental Engineering, University of Cincinnati, Cincinnati, OH, USA.

A catalyst system with dedicated selectivity toward a single hydrocarbon or oxygenate product is essential to enable the industrial application of electrochemical conversion of CO to high-value chemicals. Cu is the only known metal catalyst that can convert CO to high-order hydrocarbons and oxygenates. However, the Cu-based catalysts suffer from diverse selectivity. Here, we report that the functionalized graphene quantum dots can direct CO to CH conversion with simultaneous high selectivity and production rate. The electron-donating groups facilitate the yield of CH from CO electro-reduction while electron-withdrawing groups suppress CO electro-reduction. The yield of CH on electron-donating group functionalized graphene quantum dots is positively correlated to the electron-donating ability and content of electron-donating group. The graphene quantum dots functionalized by either -OH or -NH functional group could achieve Faradaic efficiency of 70.0% for CH at -200 mA cm partial current density of CH. The superior yield of CH on electron-donating group- over the electron-withdrawing group-functionalized graphene quantum dots possibly originates from the maintenance of higher charge density of potential active sites (neighboring C or N) and the interaction between the electron-donating group and key intermediates. This work provides insight into the design of active carbon catalysts at the molecular scale for the CO electro-reduction.
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http://dx.doi.org/10.1038/s41467-021-25640-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421353PMC
September 2021

Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.

Front Immunol 2021 16;12:731546. Epub 2021 Aug 16.

Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC) significantly, but few studies compared single ICI (SICI)-based treatments and double ICIs (DICI)-based treatments. We summarized the general efficacy of ICI-related treatments, compared the efficacy and safety of SICI-based [programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors ± chemotherapy (CT)] and DICI-based (PD-1/PD-L1 inhibitors+CTLA-4 inhibitors ± chemotherapy) treatments . CT in the first-line treatment.

Methods: We included phase II/III randomized controlled trials (RCTs), including patients with histologically confirmed stage IIIB-IV driver-gene wild-type NSCLC who received first-line ICI-related therapy in at least one arm. PubMed, Embase, and Cochrane Library were searched from January 1, 2005, to December 31, 2020. This network meta-analysis was performed in a Bayesian framework using GEMTC and JAGS package in R.3.6.1. The research was registered with PROSPERO (CRD42020184534).

Results: Twenty RCTs were involved, including 13,032 patients and 17 treatment regimens. The results showed that ICI-based therapies could provide a pooled median overall survival (mOS) (POS) of 15.79 (95% CI: 14.85-16.73) months, and there were no significant differences in OS, progression-free survival (PFS), objective response rate (ORR), and grade 3 or higher adverse events (≥3AEs) between DICI-based treatments (POS: 14.81, 12.11-17.52 months) and SICI-based treatments (POS: 16.17, 14.59-17.74 months) in overall patients. However, DICI-based treatments had significantly prolonged the OS over SICI-based treatments in squamous and PD-L1 <1% subgroups. The ranking of OS benefit by Bayesian surface under the cumulative ranking curve (SUCRA) spectrum showed that DICI+chemotherapy ranked first for overall population and subgroups including squamous, non-squamous, any level of PD-L1 expression, smoking, male, Eastern Cooperative Oncology Group performance status (ECOG PS) = 0/1, age < 65/≥65 while SICI+CT for low tumor mutation burden (TMB), non-smoking, and female subgroups, and DICI for high TMB subgroups.

Conclusions: In the first-line therapy for advanced wild-type NSCLC, both SICI- and DICI-based treatments could bring significant overall advantages over chemotherapy, with comparable outcomes of efficacy and ≥3AEs. DICI-based treatments were more effective than SICI-based treatments in squamous and PD-L1 <1% subgroups. For most populations, DICI+chemotherapy could be the best choice with a survival benefit, while SICI+chemotherapy has established its position actually.

Systematic Review Registration: [PROSPERO], identifier [CRD42020184534].
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http://dx.doi.org/10.3389/fimmu.2021.731546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415225PMC
August 2021

Regulation of fibroblast growth factor 9 on the differentiation of goat intramuscular adipocytes.

Anim Sci J 2021 Dec;92(1):e13627

Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization of Education Ministry, Southwest Minzu University, Chengdu, China.

It has been found that fibroblast growth factor receptor (FGF-FGFR) signaling can regulate the expression of adipocyte differentiation genes. FGF9 is one of the members of FGFs that mainly binds receptors FGFR2 and FGFR3. FGF9 is highly expressed in the adipose tissue of humans and mice, but there are few reports on the role of FGF9 in goat intramuscular adipocyte differentiation. Therefore, this study explored the effect of FGF9 on adipocyte differentiation through cell culture, interference, and overexpression. The expression of receptors FGFR1-FGFR4 in adipocyte differentiation and their effects on differentiation were detected to screen receptor gene of FGF9. Finally, the interaction between FGF9 and the receptor was tested by cotransfection. Our results showed that FGF9 interacts with FGFR2 to inhibit goat intramuscular adipocyte differentiation by regulating peroxisome proliferator-activated receptor gamma (PPARγ) and preadipocyte factor 1 (Pref1), which is a data support for subsequent pathway research.
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http://dx.doi.org/10.1111/asj.13627DOI Listing
December 2021

Design of Crystalline Reduction-Oxidation Cluster-Based Catalysts for Artificial Photosynthesis.

JACS Au 2021 Aug 8;1(8):1288-1295. Epub 2021 Jul 8.

School of Chemistry, South China Normal University, Guangzhou 510006, P. R. China.

Metal cluster-based compounds have difficulty finishing the photocatalytic carbon dioxide reduction reaction (CORR) and water oxidation reaction (WOR) simultaneously because of the big challenge in realizing the coexistence of independently and synergistically reductive and oxidative active sites in one compound. Herein, we elaborately designed and synthesized one kind of crystalline reduction-oxidation () cluster-based catalysts connecting reductive { } (M = Zn, Co, and Ni for , , respectively) cluster and oxidative {PMoVO} cluster through a single oxygen atom bridge to achieve artificial photosynthesis successfully. These clusters can all photocatalyze CO-to-CO and HO-to-O reactions simultaneously, of which the CO yield of is 13.8 μmol/g·h, and the selectivity is nearly 100%. Density functional theory calculations reveal that the concomitantly catalytically reductive and oxidative active sites (for CORR and WOR, respectively) and the effective electron transfer between the sites in these photocatalysts are the key factors to complete the overall photosynthesis.
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http://dx.doi.org/10.1021/jacsau.1c00186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397352PMC
August 2021

Artificial intelligence manages congenital cataract with individualized prediction and telehealth computing.

NPJ Digit Med 2020 Aug 28;3(1):112. Epub 2020 Aug 28.

Department of Ophthalmology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

A challenge of chronic diseases that remains to be solved is how to liberate patients and medical resources from the burdens of long-term monitoring and periodic visits. Precise management based on artificial intelligence (AI) holds great promise; however, a clinical application that fully integrates prediction and telehealth computing has not been achieved, and further efforts are required to validate its real-world benefits. Taking congenital cataract as a representative, we used Bayesian and deep-learning algorithms to create CC-Guardian, an AI agent that incorporates individualized prediction and scheduling, and intelligent telehealth follow-up computing. Our agent exhibits high sensitivity and specificity in both internal and multi-resource validation. We integrate our agent with a web-based smartphone app and prototype a prediction-telehealth cloud platform to support our intelligent follow-up system. We then conduct a retrospective self-controlled test validating that our system not only accurately detects and addresses complications at earlier stages, but also reduces the socioeconomic burdens compared to conventional methods. This study represents a pioneering step in applying AI to achieve real medical benefits and demonstrates a novel strategy for the effective management of chronic diseases.
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http://dx.doi.org/10.1038/s41746-020-00319-xDOI Listing
August 2020

Investigation of the Kinetics and Reaction Mechanism for Photodegradation Tetracycline Antibiotics over Sulfur-Doped BiWO/ZnInS Direct Z-Scheme Heterojunction.

Nanomaterials (Basel) 2021 Aug 20;11(8). Epub 2021 Aug 20.

National Engineering Research Center for Non-Food Biorefinery, Guangxi Key Laboratory of Bio-Refinery, Institute of Eco-Environmental Research, Guangxi Academy of Sciences, Nanning 530007, China.

The rational design of direct Z-scheme heterostructural photocatalysts using solar energy is promising for energy conversion and environmental remediation, which depends on the precise regulation of redox active sites, rapid spatial separation and transport of photoexcited charge and a broad visible light response. The BiWO materials have been paid more and more attention because of their unique photochemical properties. In this study, S doped BiWO coupled with twin crystal ZnInS nanosheets (Sov-BWO/T-ZIS) were prepared as an efficient photocatalyst by a simple hydrothermal method for the removal of tetracycline hydrochloride (TCH). Multiple methods (XRD, TEM, XPS, EPR, UV vis DRS, PL etc.) were employed to systematically investigate the morphology, structure, composition and photochemical properties of the as-prepared samples. The XRD spectrum indicated that the S ions were successfully doped into the Sov-BWO component. XPS spectra and photoelectrochemical analysis proved that S served as electronic bridge and promoted captured electrons of surface oxygen vacancies transfer to the valence band of T-ZIS. Through both experimental and in situ electron paramagnetic resonance (in situ EPR) characterizations, a defined direct Z-scheme heterojunction in S-BWO/T-ZIS was confirmed. The improved photocatalytic capability of S-BWO/T-ZIS results ascribed that broadened wavelength range of light absorption, rapid separation and interfacial transport of photoexcited charge, precisely regulated redox centers by optimizing the interfacial transport mode. Particularly, the Sov-50BWO/T-ZIS Z-scheme heterojunction exhibited the highest photodegradation rate was 95% under visible light irradiation. Moreover, this heterojunction exhibited a robust adsorption and degradation capacity, providing a promising photocatalyst for an organic pollutant synergistic removal strategy.
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http://dx.doi.org/10.3390/nano11082123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400379PMC
August 2021

A unique death pathway keeps RIPK1 D325A mutant mice in check at embryonic day 10.5.

PLoS Biol 2021 Aug 26;19(8):e3001304. Epub 2021 Aug 26.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.

Tumor necrosis factor receptor-1 (TNFR1) signaling, apart from its pleiotropic functions in inflammation, plays a role in embryogenesis as deficiency of varieties of its downstream molecules leads to embryonic lethality in mice. Caspase-8 noncleavable receptor interacting serine/threonine kinase 1 (RIPK1) mutations occur naturally in humans, and the corresponding D325A mutation in murine RIPK1 leads to death at early midgestation. It is known that both the demise of Ripk1D325A/D325A embryos and the death of Casp8-/- mice are initiated by TNFR1, but they are mediated by apoptosis and necroptosis, respectively. Here, we show that the defects in Ripk1D325A/D325A embryos occur at embryonic day 10.5 (E10.5), earlier than that caused by Casp8 knockout. By analyzing a series of genetically mutated mice, we elucidated a mechanism that leads to the lethality of Ripk1D325A/D325A embryos and compared it with that underlies Casp8 deletion-mediated lethality. We revealed that the apoptosis in Ripk1D325A/D325A embryos requires a scaffold function of RIPK3 and enzymatically active caspase-8. Unexpectedly, caspase-1 and caspase-11 are downstream of activated caspase-8, and concurrent depletion of Casp1 and Casp11 postpones the E10.5 lethality to embryonic day 13.5 (E13.5). Moreover, caspase-3 is an executioner of apoptosis at E10.5 in Ripk1D325A/D325A mice as its deletion extends life of Ripk1D325A/D325A mice to embryonic day 11.5 (E11.5). Hence, an unexpected death pathway of TNFR1 controls RIPK1 D325A mutation-induced lethality at E10.5.
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http://dx.doi.org/10.1371/journal.pbio.3001304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389420PMC
August 2021
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