Publications by authors named "Hua Zhong"

640 Publications

Evaluation of Macular and Retinal Ganglion Cell Count Estimates for Detecting and Staging Glaucoma.

Front Med (Lausanne) 2021 1;8:740761. Epub 2021 Oct 1.

The First Affiliated Hospital of Kunming Medical University, Kunming, China.

To investigate the clinical significance of macular estimated retinal ganglion cell (mRGC) and estimated retinal ganglion cell (eRGC) in the diagnosis and staging of glaucoma. This is a cross-section study. All enrolled subjects underwent standard automated perimetry (SAP) and optical coherence tomography (OCT) examination. Swedish Interactive Threshold Algorithm (SITA)-FAST detection strategy and 24-2, 10-2 detection programs were employed in SAP assessment. The visual-field parameters and OCT parameters were calculated according to three formulas to obtain the eRGC and mRGC1 or mRGC2. The efficiency of eRGC, mRGC1, and mRGC2 estimates for the staging of glaucoma was compared. The sensitivity and specificity of each parameter for diagnosis of glaucoma were analyzed using the receiver operating characteristic (ROC) curve. A total of 119 eyes were included in the analysis. Compared with the healthy controls, eRGC, mRGC1, and mRGC2 estimates were significantly decreased in patients with glaucoma. As glaucoma progressed, eRGC, mRGC1, and mRGC2 estimates were gradually reduced. In preperimetric glaucoma, mRGC1, mRGC2, and eRGC were reduced by 13.2, 14.5, and 18%, respectively. In the mild stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 28, 34, and 38%, respectively. In the advanced stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 81, 85, and 92% respectively. The proportion of retinal ganglion cell (RGC) loss in the macula was close to that outside the macula. The specificity at 95% gave a sensitivity of 95.51, 86.52, and 87.64% for eRGC, mRGC1, and mRGC2, respectively. The sensitivity of structural parameters macular ganglion cell complex thickness and retinal nerve fiber layer (RNFL) were 98.88 and 95.51%, respectively. The sensitivity of functional parameters mean deviation (24-2) and visual field index (VFI) were 80.90 and 73.03%, respectively. The area under ROC curve of mRGC1, mRGC2, and eRGC were 0.982, 0.972, and 0.995 ( < 0.0001), respectively. Estimated retinal ganglion cell, mRGC1, and mRGC2 provide value to the staging of glaucoma and better diagnostic performance. Macular RGC estimatesthat integration of both structural and functional damages in macular may serve as a sensitive indicator for assessing macular damage in glaucoma and are of importance for the diagnosis and progression management of glaucoma.
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http://dx.doi.org/10.3389/fmed.2021.740761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517246PMC
October 2021

Berberine exerts its antineoplastic effects by reversing the Warburg effect via downregulation of the Akt/mTOR/GLUT1 signaling pathway.

Oncol Rep 2021 Dec 13;46(6). Epub 2021 Oct 13.

Department of Plant Sciences, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, P.R. China.

Glucose transporter 1 (GLUT1) plays a primary role in the glucose metabolism of cancer cells. However, to the best of our knowledge, there are currently no anticancer drugs that inhibit GLUT1 function. The present study aimed to investigate the antineoplastic activity of berberine (BBR), the main active ingredient in numerous Traditional Chinese medicinal herbs, on HepG2 and MCF7 cells. The results of Cell Counting Kit‑8 assay, colony formation assay and flow cytometry revealed that BBR effectively inhibited the proliferation of tumor cells, and induced G/M cell cycle arrest and apoptosis. Notably, the results of luminescence ATP detection assay and glucose uptake assay showed that BBR also significantly inhibited ATP synthesis and markedly decreased the glucose uptake ability, which suggested that the antitumor effect of BBR may occur via reversal of the Warburg effect. In addition, the results of reverse transcription‑quantitative PCR, western blotting and immunofluorescence staining indicated that BBR downregulated the protein expression levels of GLUT1, maintained the cytoplasmic internalization of GLUT1 and suppressed the Akt/mTOR signaling pathway in both HepG2 and MCF7 cell lines. Augmentation of Akt phosphorylation levels by the Akt activator, SC79, abolished the BBR‑induced decrease in ATP synthesis, glucose uptake, GLUT1 expression and cell proliferation, and reversed the proapoptotic effect of BBR. These findings indicated that the antineoplastic effect of BBR may involve the reversal of the Warburg effect by downregulating the Akt/mTOR/GLUT1 signaling pathway. Furthermore, the results of the co‑immunoprecipitation assay demonstrated that BBR increased the interaction between ubiquitin conjugating enzyme E2 I (Ubc9) and GLUT1, which suggested that Ubc9 may mediate the proteasomal degradation of GLUT1. On the other hand, BBR decreased the interaction between Gα‑interacting protein‑interacting protein at the C‑terminus (GIPC) and GLUT1, which suggested that the retention of GLUT1 in the cytoplasm may be achieved by inhibiting the interaction between GLUT1 and GIPC, thereby suppressing the glucose transporter function of GLUT1. The results of the present study provided a theoretical basis for the application of the Traditional Chinese medicine component, BBR, for cancer treatment.
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http://dx.doi.org/10.3892/or.2021.8204DOI Listing
December 2021

Comutations in DDR Pathways Predict Atezolizumab Response in Non-Small Cell Lung Cancer Patients.

Front Immunol 2021 24;12:708558. Epub 2021 Sep 24.

Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

The presence of comutations (co-mut+) in DNA damage response and repair (DDR) pathways was associated with improved survival for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC). However, it remains unknown whether co-mut+ status could be a predictive biomarker for immunotherapy. We aimed to explore the predictive role of co-mut+ status in the efficacy of ICIs. A total of 853 NSCLC patients from OAK and POPLAR trials were included in the analyses for the relationship between co-mut status and clinical outcomes with atezolizumab treatment. In co-mut+ NSCLC patients, significantly prolonged progression-free survival (PFS) ( = 0.004) and overall survival (OS) ( < 0.001) were observed in atezolizumab over docetaxel. The interaction between co-mut status and treatment was significant for PFS ( for interaction = 0.010) and OS ( for interaction = 0.017). In patients with negative or low programmed death receptor-ligand 1 expression, co-mut+ status still predicted improved clinical outcomes from atezolizumab therapy. These findings suggested that co-mut status may be a promising predictor of ICI therapy in NSCLC.
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http://dx.doi.org/10.3389/fimmu.2021.708558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499805PMC
September 2021

Pure Mg-Al Layered Double Hydroxide Film on Magnesium Alloys for Orthopedic Applications.

ACS Omega 2021 Sep 16;6(38):24575-24584. Epub 2021 Sep 16.

Department of Orthopedics, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.

Mg alloys are promising biodegradable orthopedic implants in the future. However, poor corrosion resistance and biocompatibility limit their wide applications. In this study, a pure Mg-Al layered double hydroxide (Mg-Al LDH) film on AZ31 was prepared through combining hydrofluoric acid pretreatment and hydrothermal treatment. Electrochemical analysis and the immersion test suggested that the as-prepared Mg-Al LDH-coated sample exhibited significantly enhanced corrosion resistance. The cell culture revealed that the Mg-Al LDH film was favorable for the alkaline phosphatase activity, collagen secretion, and osteogenesis-related gene expression of MC3T3-E1. Furthermore, the LDH-coated sample was beneficial for the migration, vascular endothelial growth factor secretion, and angiogenesis-related gene expression of human umbilical vein endothelial cells. The subcutaneous implantation test demonstrated that the Mg-Al LDH film could protect the substrate from corrosion and induce milder inflammation. The femur implantation demonstrated that the Mg-Al LDH sample showed better bone regeneration and osseointegration than bare AZ31. In summary, the as-prepared pure Mg-Al LDH film is able to enhance the and performances of AZ31, indicating a promising application in the orthopedic field.
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http://dx.doi.org/10.1021/acsomega.1c03169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482458PMC
September 2021

Homoharringtonine Synergized with Gilteritinib Results in the Downregulation of Myeloid Cell Leukemia-1 by Upregulating UBE2L6 in FLT3-ITD-Mutant Acute Myeloid (Leukemia) Cell Lines.

J Oncol 2021 21;2021:3766428. Epub 2021 Sep 21.

Department of Hematology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

FMS-like tyrosine kinase 3 (FLT3) mutant acute myeloid leukemia (AML) occurs in approximately 30% of all AML patients and still has a poor prognosis. This study is directed to investigate gilteritinib in combination with homoharringtonine (HHT) on FLT3-ITD-mutant AML cell lines. In our study, we found that cell proliferation was dramatically suppressed by the combination of gilteritinib and HHT. This combination therapy decreased the mitochondrial membrane potential, finally inducing apoptosis. We demonstrated that gilteritinib downregulated the expression of FLT3 and downstream signaling, further decreased the mRNA level of myeloid cell leukemia-1 (Mcl-1). HHT and combination therapy could upregulate UBE2L6, which induced the degradation of Mcl-1 via ubiquitin-proteasome system. Knockdown of UBE2L6 could protect Mcl-1 from deprivation through the ubiquitin-proteasome system. These findings may provide a novel theoretical basis for the treatment of AML patients with FLT3-ITD mutations.
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http://dx.doi.org/10.1155/2021/3766428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478557PMC
September 2021

A pH-response chemotherapy synergistic photothermal therapy for tumor suppression and bone regeneration by mussel-inspired Mg implant.

Regen Biomater 2021 Oct 10;8(6):rbab053. Epub 2021 Sep 10.

Department of Orthopedics, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong 510080, China.

Primary malignant bone tumors can be life-threatening. Surgical resection of tumor plus chemotherapy is the standard clinical treatment. However, postoperative recovery is hindered due to tumor recurrence caused by residual tumor cells and bone defect caused by resection of tumor tissue. Herein, a multifunctional mussel-inspired film was fabricated on Mg alloy, that is, an inner hydrothermal-treated layer, a middle layer of polydopamine, and an outer layer of doxorubicin. The modified Mg alloy showed excellent photothermal effect and thermal/pH-controlled release of doxorubicin. The synergistic effect of chemotherapy and photothermal therapy enabled the modified Mg alloy to kill bone tumor and inhibit tumor growth in nude mice. Moreover, because of the controlled release of Mg ions and biocompatibility of polydopamine, the modified Mg alloy supported extracellular matrix mineralization, alkaline phosphatase activity, and bone-related gene expression in C3H10T1/2. Bone implantation model in rats verified that the modified Mg showed excellent osteointegration. These findings prove that the use of mussel-inspired multifunction film on Mg alloy offers a promising strategy for the therapy of primary malignant bone tumor.
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http://dx.doi.org/10.1093/rb/rbab053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455343PMC
October 2021

Development and clinical deployment of a smartphone-based visual field deep learning system for glaucoma detection.

NPJ Digit Med 2020 Sep 22;3(1):123. Epub 2020 Sep 22.

Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, People's Republic of China.

By 2040, ~100 million people will have glaucoma. To date, there are a lack of high-efficiency glaucoma diagnostic tools based on visual fields (VFs). Herein, we develop and evaluate the performance of 'iGlaucoma', a smartphone application-based deep learning system (DLS) in detecting glaucomatous VF changes. A total of 1,614,808 data points of 10,784 VFs (5542 patients) from seven centers in China were included in this study, divided over two phases. In Phase I, 1,581,060 data points from 10,135 VFs of 5105 patients were included to train (8424 VFs), validate (598 VFs) and test (3 independent test sets-200, 406, 507 samples) the diagnostic performance of the DLS. In Phase II, using the same DLS, iGlaucoma cloud-based application further tested on 33,748 data points from 649 VFs of 437 patients from three glaucoma clinics. With reference to three experienced expert glaucomatologists, the diagnostic performance (area under curve [AUC], sensitivity and specificity) of the DLS and six ophthalmologists were evaluated in detecting glaucoma. In Phase I, the DLS outperformed all six ophthalmologists in the three test sets (AUC of 0.834-0.877, with a sensitivity of 0.831-0.922 and a specificity of 0.676-0.709). In Phase II, iGlaucoma had 0.99 accuracy in recognizing different patterns in pattern deviation probability plots region, with corresponding AUC, sensitivity and specificity of 0.966 (0.953-0.979), 0.954 (0.930-0.977), and 0.873 (0.838-0.908), respectively. The 'iGlaucoma' is a clinically effective glaucoma diagnostic tool to detect glaucoma from humphrey VFs, although the target population will need to be carefully identified with glaucoma expertise input.
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http://dx.doi.org/10.1038/s41746-020-00329-9DOI Listing
September 2020

Germline and sporadic mTOR pathway mutations in low-grade oncocytic tumor of the kidney.

Mod Pathol 2021 Sep 20. Epub 2021 Sep 20.

Kidney Cancer Program at Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Low-grade oncocytic tumor (LOT) of the kidney is a recently described entity with poorly understood pathogenesis. Using next-generation sequencing (NGS) and complementary approaches, we provide insight into its biology. We describe 22 LOT corresponding to 7 patients presenting with a median age of 75 years (range 63-86 years) and male to female ratio 2:5. All 22 tumors demonstrated prototypical microscopic features. Tumors were well-circumscribed and solid. They were composed of sheets of tumor cells in compact nests. Tumor cells had eosinophilic cytoplasm, round to oval nuclei (without nuclear membrane irregularities), focal subtle perinuclear halos, and occasional binucleation. Sharply delineated edematous stromal islands were often observed. Tumor cells were positive for PAX8, negative for CD117, and exhibited diffuse and strong cytokeratin-7 expression. Six patients presented with pT1 tumors. At a median follow-up of 29 months, four patients were alive without recurrence (three patients had died from unrelated causes). All tumors were originally classified as chromophobe renal cell carcinoma, eosinophilic variant (chRCC-eo). While none of the patients presented with known syndromic features, one patient with multiple bilateral LOTs was subsequently found to have a likely pathogenic germline TSC1 mutation. Somatic, likely activating, mutations in MTOR and RHEB were identified in all other evaluable LOTs. As assessed by phospho-S6 and phospho-4E-BP1, mTOR complex 1 (mTORC1) was activated across all cases but to different extent. MTOR mutant LOT exhibited lower levels of mTORC1 activation, possibly related to mTORC1 dimerization and the preservation of a wild-type MTOR copy (retained chromosome 1). Supporting its distinction from related entities, gene expression analyses showed that LOT clustered separately from classic chRCC, chRCC-eo, and RO. In summary, converging mTORC1 pathway mutations, mTORC1 complex activation, and a distinctive gene expression signature along with characteristic phenotypic features support LOT designation as a distinct entity with both syndromic and non-syndromic cases associated with an indolent course.
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http://dx.doi.org/10.1038/s41379-021-00896-6DOI Listing
September 2021

Short-Term Ambient Particulate Air Pollution and Hospitalization Expenditures of Cause-Specific Cardiorespiratory Diseases in China: A Multicity Analysis.

Lancet Reg Health West Pac 2021 Oct 31;15:100232. Epub 2021 Jul 31.

Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.

Background: Ambient air pollution is leading risk factor for health burden in China. Few studies in China have investigated the economic loss related to short-term exposure to ambient PM, which could trigger acute onset of cardiorespiratory diseases within a few days.

Methods: Daily ambient air pollutants data are obtained for each city from the National Air Quality Monitoring System and daily hospitalization data are obtained from the urban employee-based basic medical insurance scheme database in 74 Chinese cities with an average coverage of 88.5 million urban employees during 2016-2017. A three-stage time-series analytic approach is used in this study to investigate the impact of short-term exposure to ambient fine particulate (PM) air pollution on hospital admissions, expenses and hospital stays of three cause-specific cardiorespiratory diseases, including lower respiratory infections (LRI), coronary heart disease (CHD) and stroke in the included cities.

Findings: Based on the time-series analysis using daily hospitalization data, 28,560 LRI cases, 54,600 CHD cases, and 23,989 stroke cases are attributable to ambient PM in the 74 cities during the study period, and the related attributable expenses are 220 million CNY (US$ 32.9 million) for LRI, 458 million CNY (US$ 68.5 million) for CHD, and 410 million CNY (US$ 65.8 million) for stroke, respectively. These attributable numbers account for 1.45% to 2.05% of total hospital admissions and 1.10% to 1.51% of total expenses for the three diseases during 2016-2017, respectively. The attributable numbers for the three cause-specific cardiorespiratory diseases would increase to 362,007 hospital admission cases and 3.68 billion CNY expenses ($US550 million) in the entire urban employee population (299 million) in China during 2016-2017, and the related direct economic loss of absence from work would be 798 million CNY (US$ 119.3 million).

Interpretation: Our results support that short-term exposure to ambient PM pollution could lead to significant health and economic impacts in China. Reducing levels of ambient PM can avoid substantial health damage and expenditures, and generate appreciable economic benefits from decreasing absence from work.

Funding: Natural Science Foundation of China (82073509, 71903010, 71903011), and the National Key Research and Development Program of China (2017YFC0211600, 2017YFC0211601).
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http://dx.doi.org/10.1016/j.lanwpc.2021.100232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342975PMC
October 2021

Clinical value of an electromagnetic navigation system for CT-guided percutaneous lung biopsy of peripheral lung lesions.

J Thorac Dis 2021 Aug;13(8):4885-4893

Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: The purpose of this study was to retrospectively evaluate the clinical value of an electromagnetic navigation system for CT-guided percutaneous lung biopsy of peripheral lung lesions.

Methods: This was a retrospective study. Patients with peripheral lung lesions in our institution between January 2019 and December 2020, who underwent lung biopsy assisted by the electromagnetic navigation system were included in Group A, and those who underwent lung biopsy using conventional CT-guided percutaneous lung biopsy were included in Group B. The general features and clinical and technical information of each patient were collected and evaluated in both groups.

Results: A total of 141 patients were included in Group A (78 males and 63 females; median age, 65 years; range, 32-79 years), and 96 patients were included in group B (57 males and 39 females; median age, 65 years; range, 34-80 years). The technical success rate was 100% in both groups. The technical efficacy rate was 92.9% and 90.6% in Groups A and B (P=0.525), respectively. There was no significant difference in surgical time and the number of CT scans between the two groups, and only grade 1-2 complications occurred in the patients.

Conclusions: The electromagnetic navigation system is an effective and safe auxiliary tool for CT-guided percutaneous lung biopsy of peripheral lung lesions.
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http://dx.doi.org/10.21037/jtd-21-395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411150PMC
August 2021

Respiratory Mechanics and Association With Inflammation in COVID-19-Related ARDS.

Respir Care 2021 Nov 14;66(11):1673-1683. Epub 2021 Sep 14.

Division of Pulmonary, Critical Care, and Sleep Medicine, New York University Grossman School of Medicine, New York, New York.

Background: The novel coronavirus-associated ARDS (COVID-19 ARDS) often requires invasive mechanical ventilation. A spectrum of atypical ARDS with different phenotypes (high vs low static compliance) has been hypothesized in COVID-19.

Methods: We conducted a retrospective analysis to identify respiratory mechanics in COVID-19 ARDS. Berlin definition was used to categorize severity of ARDS. Correlational analysis using test, chi-square test, ANOVA test, and Pearson correlation was used to identify relationship between subject variables and respiratory mechanics. The primary outcome was duration of mechanical ventilation. Secondary outcomes were correlation between fluid status, C- reactive protein, PEEP, and D-dimer with respiratory and ventilatory parameters.

Results: Median age in our cohort was 60.5 y with predominantly male subjects. Up to 53% subjects were classified as severe ARDS (median [Formula: see text] = 86) with predominantly low static compliance (median C- 25.5 mL/cm HO). The overall mortality in our cohort was 61%. The total duration of mechanical ventilation was 35 d in survivors and 14 d in nonsurvivors. High PEEP (r = 0.45, < .001) and D-dimer > 2,000 ng/dL ( = .009) correlated with significant increase in physiologic dead space without significant correlation with [Formula: see text]. Higher net fluid balance was inversely related to static compliance (r = -0.24, = .045), and elevation in C- reactive protein was inversely related to [Formula: see text] (r = -0.32, = .02).

Conclusions: In our cohort of mechanically ventilated COVID-19 ARDS subjects, high PEEP and D-dimer were associated with increase in physiologic dead space without significant effect on oxygenation, raising the question of potential microvascular dysfunction.
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http://dx.doi.org/10.4187/respcare.09156DOI Listing
November 2021

A Multimodal Hydrogel Soft-Robotic Sensor for Multi-Functional Perception.

Front Robot AI 2021 26;8:692754. Epub 2021 Aug 26.

Shenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen, China.

Soft robots, with their unique and outstanding capabilities of environmental conformation, natural sealing against elements, as well as being insensitive to magnetic/electrical effects, are ideal candidates for extreme environment applications. However, sensing for soft robots in such harsh conditions would still be challenging, especially under large temperature change and complex, large deformations. Existing soft sensing approaches using liquid-metal medium compromise between large deformation and environmental robustness, limiting their real-world applicability. In this work, we propose a multimodal solid-state soft sensor using hydrogel and silicone. By exploiting the conductance and transparency of hydrogel, we could deploy both optical and resistive sensing in one sensing component. This novel combination enables us to benefit from the measurement discrepancies between the optical and electrical signal, to extract multifunctional measurements. Following this approach, prototype solid-state soft sensors were designed and fabricated, a dedicated neural network was built to extract the sensory information. Stretching and twisting were measured using the same sensor even at large deformations. In addition, exploiting the distinctive responses against temperature change, we could estimate environmental temperatures simultaneously. Results are promising for the proposed solid-state multimodal approach of soft sensors for multifunctional perception under extreme conditions.
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http://dx.doi.org/10.3389/frobt.2021.692754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427136PMC
August 2021

Patterns of Recurrence and Survival Rate After Complete Resection of Pathological Stage N2 Small-Cell Lung Cancer.

Front Oncol 2021 27;11:675354. Epub 2021 Aug 27.

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.

The benefits of surgical resection for patients with stage N2 limited-disease small-cell lung cancer (LD-SCLC) remain controversial. This retrospective study analyzed the survival and recurrence patterns of the patients diagnosed with pathological N2 (p-N2) LD-SCLC after radical resection. A total of 171 p-N2 LD-SCLC patients who underwent radical pulmonary resection and systematic lymphadenectomies at Shanghai Chest Hospital from July 2005 to June 2015 were enrolled. The influence of the mediastinal lymph node status (single or multiple nodes, single- or multiple-station) on the survival and recurrence patterns was retrospectively analyzed. The main recurrence sites were outside the chest cavity (54.8%) and hematogenous metastasis (67.4%). The bone and liver as initial recurrence sites had a poor prognosis, with a median overall survival (OS) of 13.100 months and 11.900 months, respectively. The median disease-free survival (DFS) of patients diagnosed with single and multiple p-N2 after surgery were 19.233 and 9.367 months (P = 0.001), and the median OS were 43.033 and 17.100 months (P < 0.001), respectively. In conclusion, recurrence occurred in the form of hematogenous metastasis mostly in the extra-thoracic part. Interestingly, patients diagnosed with single p-N2 benefited from radical resection. Surgery may be a treatment option regardless of the T stage if N2 SCLC with a single metastatic lymph node can be identified preoperatively.
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http://dx.doi.org/10.3389/fonc.2021.675354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429904PMC
August 2021

Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine.

Front Immunol 2021 27;12:709986. Epub 2021 Aug 27.

Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, China.

Background: Nowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated.

Methods: The RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis.

Results: Four glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1-IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1-IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype.

Conclusions: ANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.
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http://dx.doi.org/10.3389/fimmu.2021.709986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429949PMC
August 2021

Application of Simulated Arms with Real-Time Pressure Monitor in Casting and Splinting by Physiological Sensors.

Sensors (Basel) 2021 Aug 24;21(17). Epub 2021 Aug 24.

Department of Electronic Engineering, National Taipei University of Technology, Taipei 10608, Taiwan.

In the real condition, the small sensor found it difficult to detect the position of the pressure sore because of casting displacement clinically. The large sensor will detect the incorrect pressure value due to wrinkles without close to arm. Hence, we developed a simulated arm with physiological sensors combined with an APP and a cloud storage system to detect skin pressure in real time when applying a short arm cast or splint. The participants can apply a short arm cast or splint on the simulative arm and the pressure in the cast or splint could be immediately displaced on the mobile application. The difference of pressure values from six pressure detection points of the simulated arm between the intern and the attending physician with 20-year working experience were 22.8%, -7.3%, 25.0%, 8.6%, 38.2%, 49.6%, respectively. It showed that the difference of pressure values in two farthest points, such as radius stab and ulnar styloid, was maximal. The pressures on the skin surface of the short arm cast were within acceptable range. Doctors would obtain reliable reference data and instantly understand the tightness of the swathed cast which would enable them to adjust it at any time to avoid complications.
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http://dx.doi.org/10.3390/s21175681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434106PMC
August 2021

Lactate and blood ammonia on admission as biomarkers to predict the prognosis of patients with acute mushroom poisoning and liver failure: a retrospective study.

Toxicol Res (Camb) 2021 Aug 24;10(4):850-855. Epub 2021 Jul 24.

Department of Emergency, the First Affiliated Hospital of Dalian Medical University, No.222 Zhongshan Road, Xigang District Dalian, China.

The diagnosis of liver damage induced by mushroom poisoning is still challenging. This study aims to screen the early biological indexes that could predict acute mushroom poisoning with liver damage. The patients with acute mushroom poisoning and liver damage admitted to The First Affiliated Hospital of Dalian Medical University,China from July 2007 to August 2017 were analyzed retrospectively. A total of 66 patients were enrolled in this study, with 44 and 22 patients in the liver injury group and liver failure group, respectively. Ten patients in the liver failure group died, with a mortality of 45.5% in this group. Multivariable Cox regression showed that the blood ammonia (NH3) and lactic acid (Lac) at the time of admission were independently associated with the in-hospital time to death for patients with liver failure induced by mushroom poisoning. Lactate and blood ammonia at the time of admission could be used to predict the prognosis of patients with acute mushroom poisoning and liver failure.
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http://dx.doi.org/10.1093/toxres/tfab068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403588PMC
August 2021

Network-Based Integrated Analysis of Transcriptomic Studies in Dissecting Gene Signatures for LPS-Induced Acute Lung Injury.

Inflammation 2021 Aug 30. Epub 2021 Aug 30.

College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China.

Acute lung injury (ALI) is a type of serious clinical syndrome leading to morbidity and mortality. However, the precise pathogenesis of ALI remains elusive. Here, we implemented an integrative meta-analysis of six GEO microarray studies with 76 samples in the ALI mouse model. A total of 958 differentially expressed genes (DEGs) were identified in LPS relative to normal samples. Then, a network-based meta-analysis was used to mine core DEGs and to unfold the interactions among these genes. We found that Ebi3 was the top upregulated genes in the LPS-induced ALI. GO, KEGG, and GSEA analyses were performed for functional annotation. qRT-PCR revealed augmented expression of six candidate genes (Stat1, Syk, Jak3, Rac2, Ripk1, and Traf6) in the established ALI mouse model with LPS exposure. Taken together, our study investigated comprehensively hub DEGs and their networks for LPS-stimulated ALI, which might afford an additional approach to determine biomarkers and therapeutic targets and explore the molecular pathophysiology toward ALI.
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http://dx.doi.org/10.1007/s10753-021-01518-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405180PMC
August 2021

Characterization and Tribological Performances of Graphene and Fluorinated Graphene Particles in PAO.

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

Institute of Tribology, School of Mechanical Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei 230009, China.

Graphene has been widely used as a lubricating additive to reduce the energy consumption of engines and improve fuel economy because of its unique crystal structure. Herein, graphene (GR) and fluorinated graphene (F-GR) nanoparticles were prepared by ball milling and liquid-phase exfoliation. The SEM/EDS, HRTEM, XPS, Raman spectrometer, X-ray spectrometer, FTIR were used to investigate the morphologies, surface groups, and crystal structure of two kinds of graphene materials. The influence of loads on the tribological properties of two kinds of particles was investigated in Poly Alpha Olefin (PAO6) using a UMT-2 reciprocating tribometer. Results showed that the crystal structure of GR is better than F-GR. F-GR can improve the lubrication performance of PAO6. For PAO6 containing 1 wt% F-GR at 10 N, the average friction coefficient and average wear rate decreased by 12.3% and 87% relative to pure PAO6, respectively. However, the high load resulted in an inconspicuous anti-wear and anti-friction effect. The influence of F-GR on the tribological behavior of PAO6 was more substantial than that of GR. The friction and wear mechanisms attributed to F-GR quickly entered the interface between the friction pairs. Friction-induced F-GR nanosheets mainly took the tribo-chemical reactions to participate in the lubrication film formation and helped achieve a low friction coefficient and wear rate.
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http://dx.doi.org/10.3390/nano11082126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401023PMC
August 2021

The complete chloroplast genome of cv. 'Taihang' (Fabaceae) from Shanxi, China.

Mitochondrial DNA B Resour 2021 18;6(9):2688-2690. Epub 2021 Aug 18.

College of Grassland Science, Shanxi Agricultural University, Jinzhong, Shanxi, China.

is an important perennial forage with multiple characteristics of resistance. In this study, we sequenced and characterized the complete chloroplast genome of 'Taihang', which is 124, 254 bp in length. A total of 108 genes were identified, including 74 protein-coding, 30 tRNA, and four rRNA genes. Phylogenetic analysis based on 27 chloroplast genomes showed that 'Taihang' has a close relationship with from Qinghai Province, China. The data are useful in better understanding the genetic diversity and stress resistance of and contribute to the phylogenetic study of Trifolieae.
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http://dx.doi.org/10.1080/23802359.2021.1966328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382020PMC
August 2021

Comparison of the SITA Faster-a new visual field strategy with SITA Fast strategy.

Int J Ophthalmol 2021 18;14(8):1185-1191. Epub 2021 Aug 18.

The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China.

Aim: To compare visual field defects using the Swedish Interactive Thresholding Algorithm (SITA) Fast strategy with SITA Faster strategy, a newly developed time-saving threshold visual field strategy.

Methods: Ninety-three participants (60 glaucoma patients and 33 normal controls) were enrolled. One eye from each participant was selected randomly for the study. SITA Fast and SITA Faster were performed using the 24-2 default mode for each test. The differences of visual field defects between the two strategies were compared using the test duration, false-positive response errors, mean deviation (MD), visual field index (VFI) and the numbers of depressed test points at the significant levels of <5%, <2%, <1%, and <0.5% in probability plots. The correlation between strategies was analyzed. The agreement between strategies was acquired by Bland-Altman analysis.

Results: Mean test durations were 246.0±60.9s for SITA Fast, and 156.3±46.3s for SITA Faster (<0.001). The test duration of SITA Faster was 36.5% shorter than SITA Fast. The MD, VFI and numbers of depressed points at <5%, <2%, <1%, and <0.5% in probability plots showed no statistically significant difference between two strategies (>0.05). Correlation analysis showed a high correlation for MD (=0.986, <0.001) and VFI (=0.986, <0.001) between the two strategies. Bland-Altman analysis showed great agreement between the two strategies.

Conclusion: SITA Faster, which saves considerable test time, has a great test quality comparing to SITA Fast, but may be not directly interchangeable.
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http://dx.doi.org/10.18240/ijo.2021.08.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342287PMC
August 2021

Genetic Diversity Relationship Between Grain Quality and Appearance in Rice.

Front Plant Sci 2021 2;12:708996. Epub 2021 Aug 2.

State Key Laboratory of Hybrid Rice, Key Laboratory for Research and Utilization of Heterosis in Indica Rice, Ministry of Agriculture, College of Life Sciences, Wuhan University, Wuhan, China.

Grain quality is an important breeding objective in rice, and the appearance of the grain also affects its commercial value in the market. The aim of this study was to decode the rice grain qualities and appearances, such as gelatinization temperature (GT), amylose content (AC), grain protein content (GPC), pericarp color (PC), length/width ratio (LWR), and grain volume (GV) at phenotypic and genetic levels, as well as the relationships among them. A genome-wide association study (GWAS) was used to identify the quantitative trait locus (QTLs) associated with the target traits using mixed linear model (MLM) and Bayesian-information and linkage-disequilibrium iteratively nested keyway (BLINK) methods. In general, AC was negatively correlated with GPC and GV, while it was positively correlated with LWR and PC. GPC was positively correlated with LWR. Using the rice diversity panel 1 (RDP1) population, we identified 11, 6, 2, 7, 11, and 6 QTLs associated with GT, AC, GPC, PC, LWR, and GV, respectively. Five germplasm lines, superior in grain qualities and appearances for basic breeding materials or improvement, were identified. Notably, an F-box gene was located in the linkage disequilibrium (LD) block of , which specifically expresses in endosperm and seed tissues, suggesting that this gene may regulate the seed development in rice grain. Besides, different haplotypes of showed significant differences in AC, indicating that this gene may be related to AC in rice grain.
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http://dx.doi.org/10.3389/fpls.2021.708996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365354PMC
August 2021

Multi-locus genome-wide association studies for five yield-related traits in rice.

BMC Plant Biol 2021 Aug 10;21(1):364. Epub 2021 Aug 10.

State Key Laboratory of Hybrid Rice, Key Laboratory for Research and Utilization of Heterosis in Indica Rice, Ministry of Agriculture, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China, 430072.

Background: Improving the overall production of rice with high quality is a major target of breeders. Mining potential yield-related loci have been geared towards developing efficient rice breeding strategies. In this study, one single-locus genome-wide association studies (SL-GWAS) method (MLM) in conjunction with five multi-locus genome-wide association studies (ML-GWAS) approaches (mrMLM, FASTmrMLM, pLARmEB, pKWmEB, and ISIS EM-BLASSO) were conducted in a panel consisting of 529 rice core varieties with 607,201 SNPs.

Results: A total of 152, 106, 12, 111, and 64 SNPs were detected by the MLM model associated with the five yield-related traits, namely grain length (GL), grain width (GW), grain thickness (GT), thousand-grain weight (TGW), and yield per plant (YPP), respectively. Furthermore, 74 significant quantitative trait nucleotides (QTNs) were presented across at least two ML-GWAS methods to be associated with the above five traits successively. Finally, 20 common QTNs were simultaneously discovered by both SL-GWAS and ML-GWAS methods. Based on genome annotation, gene expression analysis, and previous studies, two candidate key genes (LOC_Os09g02830 and LOC_Os07g31450) were characterized to affect GW and TGW, separately.

Conclusions: These outcomes will provide an indication for breeding high-yielding rice varieties in the immediate future.
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http://dx.doi.org/10.1186/s12870-021-03146-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353822PMC
August 2021

HO‑1 knockdown upregulates the expression of VCAM‑1 to induce neutrophil recruitment during renal ischemia‑reperfusion injury.

Int J Mol Med 2021 10 9;48(4). Epub 2021 Aug 9.

Department of Cell Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.

Heme oxygenase‑1 (HO‑1) has been reported to be upregulated following renal ischemia‑reperfusion injury (IRI) and plays a key cytoprotective role; however, the underlying molecular mechanisms of its protective effects remain poorly understood. In the present study, in order to further elucidate the molecular mechanisms underlying the cytoprotective role of HO‑1 in renal IRI, HO‑1 and HO‑1 mice were subjected to renal ischemia and subsequent reperfusion followed by the analysis of blood urea nitrogen (BUN) and serum creatinine (SCr) levels, the severity of histological changes, HO‑1 and vascular cell adhesion molecule‑1 (VCAM‑1) protein expression, the mRNA expression of inflammatory factors and the effects of VCAM‑1 blockade. The results of the present study demonstrated that the upregulated expression levels of VCAM‑1 in HO‑1 mice during IRI increased the extent of renal tissue damage and activated the inflammatory response. These effects were subsequently reversed following infusion with an anti‑VCAM‑1 antibody. In addition, the upregulated expression of VCAM‑1 in mouse glomerulus vascular endothelial cells isolated from HO‑1 mice increased the adhesion and migration of neutrophils, effects which were also reversed upon incubation with an anti‑VCAM‑1 antibody. These results indicated that HO‑1 knockdown may upregulate the expression of VCAM‑1 during renal IRI, resulting in increased neutrophil recruitment and the activation of the inflammatory response, thereby exacerbating renal IRI. The present study thus highlights the regulatory mechanisms of HO‑1 in renal IRI and provides a potential target for the clinical treatment of IRI following renal transplantation.
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http://dx.doi.org/10.3892/ijmm.2021.5018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416149PMC
October 2021

The genomic characteristics of different progression patterns in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors.

Ann Transl Med 2021 May;9(9):779

Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Fast progression (FP), hyperprogressive disease (HPD), and early death (ED) are the newly reported cancer progression patterns in response to immune checkpoint inhibitor (ICI) treatment. This study aimed to investigate the clinical and genomic characteristics of FP, HPD, and ED following the ICI treatment of advanced non-small cell lung cancer (NSCLC).

Methods: We retrospectively reviewed 117 patients with advanced NSCLC who were treated with ICIs from March 2017 to October 2019. FP was defined as (I) time to treatment failure (TTF) <1.5 months; and (II) ≥50% increase in the sum of the longest diameter (SLD) of target lesions. HPD was defined as (I) TTF <2 months; and (II) ≥50% change in tumor growth rate compared with before ICI initiation. ED was defined as overall survival (OS) <3 months. Tissue samples from 18 FP/HPD/ED patients and 5 partial response (PR) patients were subjected to genomic profiling. Genomic data from 693 tumor mutational burden- and histology-matched lung cancer samples were retrieved from an internal database as a control.

Results: FP, HPD, and ED occurred in 7.21%, 9.38%, and 11.97% patients, respectively. The progression-free survival was comparable among the 3 groups. The median overall survival for FP, HPD, and ED were 3.19, 11.2, and 1.84 months, respectively. The genomic landscape revealed 1 amplification, 1 fusion, 6 mutations, 1 amplification, 1 amplification, and 1 fusion among the 18 patients with FP/HPD/ED. Compared with the Control group, ED patients showed higher mutation frequencies for (P<0.01), (P<0.01), and (P=0.04). Mutations in (P=0.018) and (P=0.04) were more common in FP patients; HPD patients showed more frequent mutations (P<0.001).

Conclusions: We demonstrated different genomic characteristics across different progression patterns following ICI treatment, which might assist clinicians in the prediction of a patient's response, identifying candidates for more effective ICI therapy.
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http://dx.doi.org/10.21037/atm-20-6910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246171PMC
May 2021

Dissecting Prognosis Modules and Biomarkers in Glioblastoma Based on Weighted Gene Co-Expression Network Analysis.

Cancer Manag Res 2021 8;13:5477-5489. Epub 2021 Jul 8.

College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, People's Republic of China.

Introduction: As one of the most prevalent and malignant brain cancers, glioblastoma multiforme (GBM) presents a poor prognosis and the molecular mechanisms remain poorly understood. Consequently, molecular research, including various biomarkers, is essential to exploit the occurrence and development of glioma.

Methods: Weighted gene co-expression network analysis (WGCNA) was used to construct gene co-expression modules and networks based on the Chinese Glioma Genome Atlas (CGGA) glioblastoma specimens. Then, protein-protein interaction (PPI) and gene ontology (GO) analyses were performed to mine hub genes. RT-PCR and immunohistochemistry were employed to examine the expression level of GRPR, CXCL5, and CXCL11 in glioma patients.

Results: We confirmed two gene modules by protein-protein interaction networks. Functional enrichment analysis was performed to identify the significance of gene modules. Prognostic biomarkers , and related to the survival time of GBM samples were mined in The Cancer Genome Atlas (TCGA) dataset. qRT-PCR revealed that , and led to a significant increase in GBM sample compared to control.

Conclusion: In this study, we developed and confirmed three mRNA signatures (GRPR, CXCL5, and CXCL11) for evaluating overall survival in GBM patients. Our research assists in existing understanding of GBM diagnosis and prognosis.
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http://dx.doi.org/10.2147/CMAR.S310346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276137PMC
July 2021

UDP--Acetylglucosamine Pyrophosphorylase 2 (UAP2) and 1 (UAP1) Perform Synergetic Functions for Leaf Survival in Rice.

Front Plant Sci 2021 24;12:685102. Epub 2021 Jun 24.

Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Jiangxi Agricultural University, Ministry of Education of the People's Republic of China, Nanchang, China.

Functional inactivation of UDP--acetylglucosamine pyrophosphorylase 1 (UAP1) induces defense response-related lesion-mimic spots and subsequent early senescence in every newly grown leaf of the rice mutant after a short period's normal growth. However, the molecular mechanism of these leaves sustaining the short period's survival is still unknown. Phenotypic and molecular studies show that defense response-related lesion-mimic spots and early leaf senescence appear on the normally grown leaf and aggravate with the growth time. Bioinformatic analysis reveals that UAP proteins are evolutionarily conserved among eukaryotes, and there exists UAP2 protein except UAP1 protein in many higher organisms, including rice. Rice UAP2 and UAP1 proteins present high sequence identities and very similar predicted 3D structures. Transcriptional expression profile of the gene decreases with the appearance and aggravating of leaf spots and early senescence of , implying the role of the gene in maintaining the initial normal growth of leaves. Enzymatic experiments verified that the UAP2 protein performs highly similar UAP enzymatic activity with the UAP1 protein, catalyzing the biosynthesis of UDP-GlcNAc. And these two UAP proteins are found to have the same subcellular localization in the cytoplasm, where they most presumably perform their functions. Overexpression of the gene in plants succeeds to rescue their leaf mutant phenotype to normal, providing direct evidence for the similar function of the gene as the gene. The gene is mainly expressed in the young leaf stage for functions, while the gene is highly expressed during the whole leaf developmental stages. Based on these findings, it is suggested that and play key roles in rice leaf survival during its development in a synergetic manner, protecting the leaf from early senescence.
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http://dx.doi.org/10.3389/fpls.2021.685102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264299PMC
June 2021

Diagnosis analysis of rectal function through using ensemble empirical mode decomposition-deep belief networks algorithm.

Rev Sci Instrum 2021 Jun;92(6):064102

Shanghai Key Laboratory of Power Station Automation Technology, School of Mechatronics Engineering and Automation, Shanghai University, Shanghai 200444, China.

The rectal motility function can reflect a person's rectal health status. To diagnose the rectal motility function after artificial anal sphincter implantation, this paper proposes a rectal function diagnosis model based on ensemble empirical mode decomposition-deep belief networks (EEMD-DBNs). Because of the rectal pressure signals that are unstable and subjected to noise interferences, an EEMD framework based on EMD, which can reduce the effect of signal modal mixing, is proposed. EMD and EEMD were used to decompose the analog signal, respectively, and it was found that EEMD can significantly reduce the effect of mode aliasing. During the rectal pressure signal decomposition experiment, by analyzing the intrinsic mode functions generated by the signals from normal people and diseased patients, the rectal signals at these two different conditions can be well distinguished. Additionally, the DBN was introduced to perform deep learning to extract the multi-dimensional features of rectal signals and then output the classification results via using the top-level classifier, which can overcome the difficulties in extracting the rectal signal features. The results showed that, following the principle of balancing the diagnosis accuracy and model running speed, the best diagnosis performance was achieved when three restricted Boltzmann machines and five layers of DBN model were set, with the diagnosis rate of 85%. The diagnostic model used in this study can distinguish the signals between normal and abnormal rectal functions with accurate performance, thus providing the technical support for the recovery of the rectal motility function of artificial anal sphincter implanters.
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http://dx.doi.org/10.1063/5.0042382DOI Listing
June 2021

Time Varying Mixed Effects Model with Fused Lasso Regularization.

J Appl Stat 2021 10;48(8):1513-1526. Epub 2020 Jul 10.

Department of Industrial and Management Engineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon, 22012, Republic of Korea.

The associations between covariates and the outcomes often vary over time, regardless of whether the covariate is time-varying or time-invariant. For example, we hypothesize that the impact of chronic diseases, such as diabetes and heart disease, on people's physical functions differ with aging. However, the age-varying effect would be missed if one models the covariate simply as a time-invariant covariate (yes/no) with a time-constant coefficient. We propose a fused lasso-based time-varying linear mixed effect (FTLME) model and an efficient two-stage parameter estimation algorithm to estimate the longitudinal trajectories of fixed-effect coefficients. Simulation studies are presented to demonstrate the efficacy of the method and its computational efficiency in estimating smooth time-varying effects in high dimensional settings. A real data example on the Health and Retirement Study (HRS) analysis is used to demonstrate the practical usage of our method to infer age-varying impact of chronic disease on older people's physical functions.
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http://dx.doi.org/10.1080/02664763.2020.1791805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259314PMC
July 2020

Association of 25-hydroxyvitamin D level with survival outcomes in female breast cancer patients: A meta-analysis.

J Steroid Biochem Mol Biol 2021 09 30;212:105947. Epub 2021 Jun 30.

Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250014, China. Electronic address:

Conflicting results have been reported on the association of blood vitamin D level with prognosis in women with breast cancer. This meta-analysis aimed to evaluate the association between blood 25-hydroxyvitamin D level and survival outcomes in female breast cancer patients. Two authors independently searched PubMed and Embase databases from their inception to August 25, 2020. Prospective or retrospective cohort studies evaluating the association between blood 25-hydroxyvitamin D level and survival outcomes in women with breast cancer were included. Outcome measures included overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). Twelve studies involving 8574 female breast cancer patients were identified and analyzed. When compared the lowest with the highest category of 25-hydroxyvitamin D level, the pooled adjusted hazard ratio (HR) was 1.57 (95 % confidence interval [CI] 1.35-1.83) for OS, 1.98 (95 % CI 1.55-2.53) for DFS, and 1.44 (95 % CI 1.14-1.81) for BCSS. This meta-analysis indicates that lower blood 25-hydroxyvitamin D level is significantly associated with reduced survival among female breast cancer patients. Additional clinical trials are required to investigate whether vitamin D supplement can improve survival outcomes in these patients.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105947DOI Listing
September 2021

Global Analysis of UDP Glucose Pyrophosphorylase (UDPGP) Gene Family in Plants: Conserved Evolution Involved in Cell Death.

Front Plant Sci 2021 10;12:681719. Epub 2021 Jun 10.

Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education of the People's Republic of China, Jiangxi Agricultural University, Nanchang, China.

UDP glucose pyrophosphorylase (UDPGP) family genes have been reported to play essential roles in cell death or individual survival. However, a systematic analysis on UDPGP gene family has not been performed yet. In this study, a total of 454 UDPGP proteins from 76 different species were analyzed. The analyses of the phylogenetic tree and orthogroups divided UDPGPs into three clades, including UDP--acetylglucosamine pyrophosphorylase (UAP), UDP-glucose pyrophosphorylase (UGP, containing UGP-A and UGP-B), and UDP-sugar pyrophosphorylase (USP). The evolutionary history of the UDPGPs indicated that the members of UAP, USP, and UGP-B were relatively conserved while varied in UGP-A. Homologous sequences of UGP-B and USP were found only in plants. The expression profile of UDPGP genes in was mainly motivated under jasmonic acid (JA), abscisic acid (ABA), cadmium, and cold treatments, indicating that UDPGPs may play an important role in plant development and environment endurance. The key amino acids regulating the activity of UDPGPs were analyzed, and almost all of them were located in the NB-loop, SB-loop, or conserved motifs. Analysis of the natural variants of UDPGPs in rice revealed that only a few missense mutants existed in coding sequences (CDSs), and most of the resulting variations were located in the non-motif sites, indicating the conserved structure and function of UDPGPs in the evolution. Furthermore, alternative splicing may play a key role in regulating the activity of UDPGPs. The spatial structure prediction, enzymatic analysis, and transgenic verification of UAP isoforms illustrated that the loss of N- and C-terminal sequences did not affect the overall 3D structures, but the N- and C-terminal sequences are important for UAP genes to maintain their enzymatic activity. These results revealed a conserved UDPGP gene family and provided valuable information for further deep functional investigation of the UDPGP gene family in plants.
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http://dx.doi.org/10.3389/fpls.2021.681719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222925PMC
June 2021
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