Publications by authors named "Hui Zhang"

6,728 Publications

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Toward the Cure of Acute Lymphoblastic Leukemia in Children in China.

JCO Glob Oncol 2021 Jul;7:1176-1186

Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

This study explored results of therapy of children with acute lymphoblastic leukemia (ALL) in China, recent progress, and challenges. Included are a survey of therapy outcomes of ALL in Chinese children nationwide, comparison of these data with global ALL therapy outcomes, analyses of obstacles to improving outcomes, and suggestions of how progress can be achieved. Therapy outcomes at many Chinese pediatric cancer centers are approaching those of resource-rich countries. However, nationwide outcomes still need improvement. Obstacles include suboptimal clinical trials participation, children without adequate health care funding, human resource shortages, especially physicians expert in pediatric hematology and oncology, and social-economic disparities. We suggest how these obstacles have been and continue to be remedied including expanded access to protocol-based therapy, improved supportive care, health care reforms, recruitment of trained personnel, and international collaborations. China has made substantial progress treating children with ALL. We envision even better outcomes in the near future.
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http://dx.doi.org/10.1200/GO.21.00049DOI Listing
July 2021

Mifepristone inhibited the expression of B7-H2, B7-H3, B7-H4 and PD-L2 in adenomyosis.

Reprod Biol Endocrinol 2021 Jul 21;19(1):114. Epub 2021 Jul 21.

Department of Obstetrics and Gynaecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People's Republic of China.

Background: The immune mechanism was shown to be involved in the development of adenomyosis. The aim of the current study was to evaluate the expression of the immune checkpoints B7-H2, B7-H3, B7-H4 and PD-L2 in adenomyosis and to explore the effect of mifepristone on the expression of these immune checkpoints.

Methods: The expression of B7-H2, B7-H3, B7-H4 and PD-L2 in normal endometria and adenomyosis patient samples treated with or without mifepristone was determined by immunohistochemistry analysis.

Results: In adenomyosis patient samples, the expression of B7-H2, B7-H3 and B7-H4 was increased in the eutopic and ectopic endometria compared with normal endometria, both in the proliferative and secretory phases. Moreover, the expression of B7-H2 and B7-H3 was higher in adenomyotic lesions than in the corresponding eutopic endometria, both in the proliferative and secretory phases. The expression of PD-L2 was higher in adenomyotic lesions than in normal endometria in both the proliferative and secretory phases. In the secretory phase but not the proliferative phase, the expression of B7-H4 and PD-L2 in adenomyotic lesions was significantly higher than that in the corresponding eutopic endometria. In normal endometria and eutopic endometria, the expression of B7-H4 was elevated in the proliferative phase compared with that in the secretory phase, while in the ectopic endometria, B7-H4 expression was decreased in the proliferative phase compared with the secretory phase. In addition, the expression of B7-H2, B7-H3, B7-H4 and PD-L2 was significantly decreased in adenomyosis tissues after treatment with mifepristone.

Conclusions: The expression of the immune checkpoint proteins B7-H2, B7-H3, B7-H4 and PD-L2 is upregulated in adenomyosis tissues and is downregulated with mifepristone treatment. The data suggest that B7 immunomodulatory molecules are involved in the pathophysiology of adenomyosis.
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http://dx.doi.org/10.1186/s12958-021-00800-6DOI Listing
July 2021

Association of Admission NIHSS Score with Infarct Core Volume and Target Mismatch of Infarct Core/Penumbra Volume on CT Perfusion in Acute Ischaemic Stroke.

Cerebrovasc Dis 2021 Jul 21:1-7. Epub 2021 Jul 21.

Department of Neurology and Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China.

Introduction: Neurological impairment is associated with collateral status in acute ischaemic stroke (AIS). We aimed to validate the association between admission National Institutes of Health Stroke Scale (aNIHSS) score and infarct core volume (ICV) and target infarct core/penumbra volume mismatch (TMM) on CT perfusion (CTP) in AIS patients.

Methods: Patients with acute middle cerebral artery or internal carotid artery occlusion from 2011 to 2020 were included. All patients underwent pretreatment CTP at admission. ICV and TMM were analyzed with MIStar software on CTP maps. aNIHSS scores and clinical characteristics of patients were obtained from our prospectively recorded stroke database.

Results: We recruited 182 patients with a median age of 69.5 years; 85 (63.7%) were male, and the median aNIHSS score was 14. Of those, 149 (81.8%) had an ICV < 70 mL, and 139 (76.3%) had TMM. Lower aNIHSS was associated with an ICV < 70 mL, with an area under the curve (AUC) of 0.74, and TMM with an AUC of 0.76. Among all 15 items of the aNIHSS, the gaze score was the only item independently associated with an ICV < 70 mL (adjusted odds ratio [OR] = 0.42, 95% confidence interval [CI]: 0.22-0.79, p = 0.008) and TMM (adjusted OR = 0.5, 95% CI: 0.28-0.9, p = 0.021). One or both aNIHSS ≤ 16 and gaze score = 0 predicted TMM with a sensitivity of 0.79 and a specificity of 0.62.

Conclusion: aNIHSS may be a useful tool to predict an ICV < 70 mL and TMM on CTP in AIS patients.
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http://dx.doi.org/10.1159/000515167DOI Listing
July 2021

Intragenic Heterochromatin-mediated Alternative Polyadenylation Modulates MiRNA and Pollen Development in Rice.

New Phytol 2021 Jul 21. Epub 2021 Jul 21.

Shanghai Center for Plant Stress Biology and Center of Excellence in Molecular Plant Sciences, Chinese Academy of Science, Shanghai, 201602, China.

Despite a much higher proportion of intragenic heterochromatin-containing genes in crop genomes, the importance of intragenic heterochromatin in crop development remains unclear. Intragenic heterochromatin can be recognized by a protein complex, ASI1-AIPP1-EDM2 (AAE) complex, to regulate alternative polyadenylation. Here, we investigated the impact of rice ASI1 on global poly(A) site usage through poly(A) sequencing and ASI1-dependent regulation on rice development. We found that OsASI1 is essential for rice pollen development and flowering. OsASI1 dysfunction has an important impact on global poly(A) site usage, which is closely related to heterochromatin marks. Intriguingly, OsASI1 interacts with the intronic heterochromatin of OsXRNL, a nuclear XRN family exonuclease gene involved in the processing of miRNA precursor, to promote the processing of full-length OsXRNL and regulates miRNA abundance. We found that OsASI1-mediated regulation of pollen development partially depends on OsXRNL. Finally, we characterized rice AAE complex and its involvement in alternative polyadenylation and pollen development. Our findings help to elucidate an epigenetic mechanism governing miRNA abundance and rice development, and provide a valuable resource for studying the epigenetic mechanisms of many important processes in crops.
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http://dx.doi.org/10.1111/nph.17635DOI Listing
July 2021

Interactive effects of childhood maltreatment and tonic respiratory sinus arrhythmia on young adults' depressive symptoms.

Psychophysiology 2021 Jul 20:e13900. Epub 2021 Jul 20.

School of Psychology, Capital Normal University, Beijing, China.

The goal of the current study was to investigate the moderating effect of tonic respiratory sinus arrhythmia (RSA) in the relation between childhood maltreatment and depression symptoms among young adults. A total of 98 participants (70 women) aged 17-22 years completed questionnaires on childhood maltreatment and depressive symptoms. RSA data were obtained during a resting condition in the laboratory. Results indicated that childhood maltreatment interacted with tonic RSA to predict depressive symptoms, even after controlling for age and body mass index (BMI) of each participant. Specifically, higher levels of childhood maltreatment were associated with higher levels of depressive symptoms, but only among young adults who exhibited lower tonic RSA. The results indicated that the association between childhood maltreatment and depressive symptoms depends on young adults' physiological functioning/flexibility. Findings suggest that consideration of external environmental factors in combination with internal physiological factors is critical to understand young adults' mental health.
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http://dx.doi.org/10.1111/psyp.13900DOI Listing
July 2021

Development of a DNA damage model that accommodates different cellular oxygen concentrations and radiation qualities.

Med Phys 2021 Jul 20. Epub 2021 Jul 20.

Department of Engineering Physics, Tsinghua University, Beijing, 100084, China.

Purpose: Research regarding cellular responses at different oxygen concentrations (OCs) is of immense interest within the field of radiobiology. Therefore, this study aimed to develop a mechanistic model to analyze cellular responses at different OCs.

Methods: A DNA damage model (the different cell oxygen level DNA damage [DICOLDD] model) that examines the oxygen effect was developed based on the oxygen fixation hypothesis, which states that dissolved oxygen can modify the reaction kinetics of DNA-derived radicals generated by ionizing radiation. The generation of DNA-derived radicals was simulated using the Monte Carlo method. The decay of DNA-derived radicals due to the competing processes of chemical repair, oxygen fixation, and intrinsic damaging using differential equations. The DICOLDD model was fitted to previous experimental data obtained under different irradiation configurations and validated by calculating yields of DNA double strand breaks (DSBs) after exposure to Cs as well as cell survival fractions (SFs) using a mechanistic model of cellular survival. Moreover, we used the DICOLDD model to calculate DNA DSB damage yields after irradiation with 0.5-50 MeV protons.

Results: Generally, DSB yields calculated after exposure to Cs at different OCs correspond to statistical uncertainties of previous experimental results. Calculated SFs of CHO and V79 cells exposed to photons, protons, and alpha particles at different OCs generally concur with those obtained in previous studies. Our results demonstrated that the variation in DSB yields was less than 10% when the cellular OC decreased from 21% to 5%. Additionally, DSB yields changed drastically when OC dropped below 1%.

Conclusions: We developed a DNA damage model to evaluate the oxygen effect and provide evidence that a reaction-kinetic model of DNA-derived radicals induced by ionizing radiation suffices to explain the observed oxygen effects. Therefore, the DICOLDD model is a powerful tool for the analysis of cellular responses at different OCs after exposure to different types of radiation.
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http://dx.doi.org/10.1002/mp.15111DOI Listing
July 2021

Clinical and Molecular Characteristics of Carbapenem-Resistant Hypervirulent Isolates in a Tertiary Hospital in Shanghai, China.

Infect Drug Resist 2021 14;14:2697-2706. Epub 2021 Jul 14.

Department of Clinical Laboratory Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, People's Republic of China.

Background: The convergence of carbapenem-resistance and hypervirulence in has led to a significant public health challenge. In recent years, there have been more and more reports on carbapenem-resistant hypervirulent (CR-hvKP) isolates.

Materials And Methods: Clinical data of patients infected with CR-hvKP from January 2019 to December 2020 in a tertiary hospital were retrospectively evaluated. The number of isolates of , hypermucoviscous (hmKP), carbapenem-resistant hypermucoviscous (CR-hmKP) and carbapenem-resistant hypervirulent (CR-hvKP) collected during the period of 2 years was calculated. The antimicrobial resistance gene, virulence-associated gene, capsular serotype gene and multilocus sequence typing (MLST) of CR-hvKP isolates were detected by PCR.

Results: During the study period, a total of 1081 isolates of non-repeat were isolated, including 392 isolates of hypermucoviscous (36.3%), 39 isolates of CR-hmKP (3.6%), and 16 isolates of CR-hvKP (1.5%). About 31.2% (5/16) of CR-hvKP were isolated from 2019, and 68.8% (11/16) of CR-hvKP were isolated from 2020. Among the 16 isolates of CR-hvKP, 13 isolates were ST11 and serotype K64, 1 isolate was ST11 and serotype K47, 1 isolate was ST23 and serotype K1, and 1 isolate was ST86 and serotype K2. The virulence-associated genes were present in all of 16 CR-hvKP isolates, followed by (n=14), rmpA (n=13), aerobactin (n=2), allS (n=1). Sixteen CR-hvKP isolates all carry carbapenemase gene and extended-spectrum β-lactamase gene . ERIC-PCR DNA fingerprinting results showed that 16 CR-hvKP isolates were highly polymorphic, and there were significant differences in bands among the isolates, presenting a sporadic state.

Conclusion: Although CR-hvKP was sporadically distributed, it showed an increasing trend year by year. Therefore, clinical attention should be paid, and necessary measures should be taken to avoid the cloning and transmission of superbacterium CR-hvKP.
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http://dx.doi.org/10.2147/IDR.S321704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286785PMC
July 2021

Enhanced biohydrogen production from corn straw by basalt fiber addition.

Bioresour Technol 2021 Jul 13;338:125528. Epub 2021 Jul 13.

Key Laboratory of New Materials and Facilities for Rural Renewable Energy of Ministry of Agriculture and Rural Affairs, College of Mechanical & Electrical Engineering, Henan Agricultural University, Zhengzhou 450002, China; Henan International Joint Laboratory of Biomass Energy and Nanomaterials, Henan Agricultural University, Zhengzhou 450002, China; Henan Collaborative Innovation Center of Biomass Energy, Henan Agricultural University, Zhengzhou 450002, China. Electronic address:

The aim of this work was to study the impact of basalt fiber (BF) on hydrogen fermentation of corn straw. The maximum of hydrogen yield and corn straw conversion rate respectively achieved 323.94 mL and 5.23% by adding 1.5 g/L BF particle with the size of 300-400 mesh, which increased by 15.74% and 15.6% respectively than control group. The BF could promote the growth of photosynthetic bacteria, subsequently influencing the products distribution and hydrogen generation. Overall, this investigation demonstrated that BF addition is an effective way to enhance biohydrogen production from corn straw.
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http://dx.doi.org/10.1016/j.biortech.2021.125528DOI Listing
July 2021

An open-label single-arm phase II study of regorafenib for the treatment of angiosarcoma.

Eur J Cancer 2021 Jul 17;154:201-208. Epub 2021 Jul 17.

Siteman Cancer Center, St Louis, MO, USA; Washington University in St. Louis School of Medicine, St Louis MO, USA; St Louis Children's Hospital, Department id Pediatrics, St Louis, MO, 63110, USA.

Purpose: Angiosarcomas represents a diverse group of aggressive high-grade vascular tumours with limited therapeutic options. We sought to determine the safety and efficacy of regorafenib, a small-molecule multikinase inhibitor, in the treatment of metastatic or locally advanced unresectable angiosarcoma.

Patients And Methods: In this single-arm multicentre, open-label phase II clinical trial, 31 patients were enrolled and received regorafenib 160 mg PO daily for 21 days of a 28-day cycle. The primary endpoint for the study was progression-free survival at 4 months. Secondary endpoints included overall survival, response rate, and safety. Patients (≥18 years) with an Eastern Cooperative Oncology Group (ECOG) score of 0-1, a life expectancy of at least 4 months who had progressed on at least one but no more than 4 prior lines of therapy were eligible.

Results: Of the 23 patients evaluable for efficacy, 2 had a complete response (8.7%), and 2 had a partial response (8.7%), for a total overall response rate of 17.4%. Median PFS was 5.5 months, and 12/23 patients (52.2%) had a PFS of greater than 4 months. 10/31 (32.3%) patients evaluable for toxicity had a grade 3 or higher adverse events.

Conclusions: Regorafenib is a safe and active treatment for refractory metastatic and unresectable angiosarcoma. Rates of adverse events were comparable to prior studies of regorafenib for other tumour types. Regorafenib, the single agent, could be considered as therapy for patients with metastatic or unresectable AS.
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http://dx.doi.org/10.1016/j.ejca.2021.06.027DOI Listing
July 2021

Aging Effect on Mandarin Chinese Vowel and Tone Identification in Six-Talker Babble.

Am J Audiol 2021 Jul 20:1-15. Epub 2021 Jul 20.

School of Foreign Languages, Tongji University, Shanghai, China.

Purpose The purpose of this study was to measure Mandarin Chinese vowel-plus-tone identification in quiet and noise for younger and older listeners. Method Two types of noise served as the masker, namely, six-talker babble and babble-modulated noise, at two signal-to-noise ratios (SNRs) of -4 and -8 dB. Fourteen listeners from both age groups were recruited, and three sets of data analyses were conducted: the identification of vowel plus tone, the identification of vowel, and the identification of tone. Results Younger listeners outperformed older listeners in all listening conditions, whereas the younger-older listener difference became greater in noise than in quiet, indicating a more detrimental effect of noise for older listeners than for younger listeners. In addition, vowel identification showed slightly better scores than tone identification in noise, suggesting that noise appeared to affect tone perception more negatively than vowel perception in Mandarin Chinese. At -4 dB SNR, there was a significantly greater amount of informational masking (IM) and a greater amount of energetic masking (EM) for older listeners than for younger listeners. At -8 dB SNR, there was a greater amount of EM for older listeners than for younger listeners but with no group difference in the amount of IM. Conclusion These results suggest that older listeners received a more negative impact of noise for Mandarin Chinese phonemic and tone recognition and had a larger amount of IM or EM from competing speech noise than younger listeners, depending on the SNR.
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http://dx.doi.org/10.1044/2021_AJA-20-00139DOI Listing
July 2021

Improvement of a SARS-CoV-2 vaccine by enhancing the conjugation efficiency of the immunogen to self-assembled nanoparticles.

Cell Mol Immunol 2021 Jul 19. Epub 2021 Jul 19.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of the Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agents and Immunotechnology, Engineering Research Center of Gene Vaccines of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.

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http://dx.doi.org/10.1038/s41423-021-00736-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287548PMC
July 2021

MicroRNA miR-215-5p regulates doxorubicin-induced cardiomyocyte injury by targeting ZEB2.

J Cardiovasc Pharmacol 2021 Jul 16. Epub 2021 Jul 16.

Department of Cardiovascular Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei, China.

Abstract: Doxorubicin (DOX) is a chemotherapeutic drug for treating various cancers. However, the DOX-induced cardiotoxicity greatly limits its clinical application. MicroRNAs (miRNAs) are emerged as critical mediators of cardiomyocyte injury. This work explored the function of miR-215-5p in the regulation of DOX-induced mouse HL-1 cardiomyocyte injury. An in vitro model of DOX-treated cardiotoxicity was established in HL-1 cells. Gene expression was measured by RT-qPCR. Cell viability was detected using CCK-8. Cell death and apoptosis were tested using TUNEL, flow cytometry, and caspase 3/7 activity assays. Luciferase reporter assay was used to examine the target of miR-215-5p. We found that DOX induced cardiomyocyte injury and upregulated miR-215-5p in HL-1 cells. Inhibition of miR-215-5p attenuated DOX-induced cardiomyocyte death and apoptosis in vitro. Mechanistical experiments indicated that ZEB2 was targeted by miR-215-5p. Additionally, ZEB2 expression was reduced in DOX-treated HL-1 cells. Rescue assays indicated that ZEB2 knockdown reversed the effects of miR-215-5p inhibition. In conclusion, miR-215-5p inhibition protects HL-1 cells against DOX-induced injury by upregulating ZEB2 expression.
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http://dx.doi.org/10.1097/FJC.0000000000001110DOI Listing
July 2021

The Patterns and Predictors of Loneliness for the Chinese Medical Students Since Post-Lockdown to New Normal With COVID-19.

Front Public Health 2021 1;9:679178. Epub 2021 Jul 1.

School of Nursing, Harbin Medical University, Harbin, China.

The coronavirus disease 2019 (COVID-19)-related quarantine has had unique psychological challenges for medical students, particularly loneliness. In this study, we demonstrated the patterns and predictors of loneliness in medical students since post-lockdown to new normal with COVID-19. A convenience sampling method was used in this study. Face-to-face online questionnaires of UCLA Loneliness Scale and psychological characteristics scales were completed by 1,478 participants. Latent profile analysis and multinominal logistic regressions were performed. Three latent profile models were identified in this study: low loneliness (52.3%), interpersonal sensitivity loneliness (3.5%), and high loneliness (44.1%). Sophomore (Est = 1.937; < 0.05) and junior students (Est = 2.939; < 0.05), neuroticism (Est = 2.475; < 0.05), high arousal symptoms (Est = 2.618; < 0.01), and the quality of support from friends (Est = 2.264; < 0.05) were the risk factors for high loneliness profile. In addition, sophomore (Est = 2.065; < 0.05) and junior students (Est = 2.702; < 0.01), openness (Est = 2.303; < 0.05), and conscientiousness personality (Est = -2.348; < 0.05) were the predictors of an interpersonal sensitive loneliness profile. Good peer relationship (Est = -2.266; < 0.05) and other support (Est = -2.247; < 0.05) were protective factors for low loneliness profile. Participants were selected from one medical university; the generalizability is limited. Timely loneliness-focused interventions should be targeted on the different profiles and predictors of loneliness in medical students.
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http://dx.doi.org/10.3389/fpubh.2021.679178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281249PMC
July 2021

Innovative color jet 3D printing of levetiracetam personalized paediatric preparations.

Asian J Pharm Sci 2021 May 1;16(3):374-386. Epub 2021 Mar 1.

Department of Pharmaceutics, Institute of Pharmacology and Toxicology of Academy of Military Medical Sciences, Beijing 100850, China.

3D printing is a promising technology used in the fabrication of complex oral dosage delivery pharmaceuticals. This study first reports an innovative color jet 3D printing (CJ-3DP) technology to produce colorful cartoon levetiracetam pediatric preparations with high accuracy and reproducibility. For this study, the ideal printing ink consisted of 40% (v/v) isopropanol aqueous solution containing 0.05% (w/w) polyvinylpyrrolidone and 4% (w/w) glycerin, which was satisfied with scale-up of the production. The external and internal spatial structures of the tablets were designed to control the appearance and release, and cartoon tablets with admirable appearances and immediate release characteristics were printed. The dosage model showed a good linear relationship between the model volume and the tablet strength ( > 0.999), which proved the potential of personalized administration. The surface roughness indicated that the appearance of the CJ-3DP tablets was significantly better than the first listed 3D printed drug (Spritam). Moreover, the scanning electron microscopy and porosity results further showed that the tablets have a structure of loose interior and tight exterior, which could ensure good mechanical properties and rapid dispersion characteristics simultaneously. In conclusion, the innovative CJ-3DP technology can be used to fabricate personalized pediatric preparations for improved compliance. Due to the stable formulation and fabrication process, this technology has the potential in scale-up production.
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http://dx.doi.org/10.1016/j.ajps.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261256PMC
May 2021

Functional Traits Are Good Predictors of Tree Species Abundance Across 101 Subtropical Forest Species in China.

Front Plant Sci 2021 30;12:541577. Epub 2021 Jun 30.

Key Laboratory of Vegetation Restoration and Management of Degraded Ecosystems, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, China.

What causes variation in species abundance for a given site remains a central question in community ecology. Foundational to trait-based ecology is the expectation that functional traits determine species abundance. However, the relative success of using functional traits to predict relative abundance is questionable. One reason is that the diversity in plant function is greater than that characterized by the few most commonly and easily measurable traits. Here, we measured 10 functional traits and the stem density of 101 woody plant species in a 200,000 m permanent, mature, subtropical forest plot (high precipitation and high nitrogen, but generally light- and phosphorus-limited) in southern China to determine how well relative species abundance could be predicted by functional traits. We found that: (1) leaf phosphorus content, specific leaf area, maximum CO assimilation rate, maximum stomata conductance, and stem hydraulic conductivity were significantly and negatively associated with species abundance, (2) the ratio of leaf nitrogen content to leaf phosphorus content () and wood density were significantly positively correlated with species abundance; (3) neither leaf nitrogen content nor leaf turgor loss point were related to species abundance; (4) a combination of and maximum stomata conductance accounted for 44% of the variation in species' abundances. Taken together, our findings suggested that the combination of these functional traits are powerful predictors of species abundance. Species with a resource-conservative strategy that invest more in their tissues are dominant in the mature, subtropical, evergreen forest.
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http://dx.doi.org/10.3389/fpls.2021.541577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278196PMC
June 2021

Enhanced recovery after surgery pathway reduces the length of hospital stay without additional complications in lumbar disc herniation treated by percutaneous endoscopic transforaminal discectomy.

J Orthop Surg Res 2021 Jul 17;16(1):461. Epub 2021 Jul 17.

Department of Orthopaedic Surgery, Minhang Hospital, Fudan University, 170 Xin Song Road, Shanghai, People's Republic of China.

Background: Enhanced recovery after surgery (ERAS) pathway in spine surgery is increasingly popular which can reduce the length of hospital stay (LOS). However, there are few studies on the safety and effectiveness of ERAS pathway in the treatment of single-level lumbar disc herniation (LDH) by percutaneous endoscopic transforaminal discectomy (PETD). The aim of this study was to investigate whether ERAS can reduce LOS of patients with single segment LDH treated by PETD.

Methods: We reviewed the outcomes of all LDH patients (L4/5) who had been treated with PETD at our institution. Quasi-experimental study was adopted between patients treated in an ERAS after PETD with those rehabilitated on a traditional pathway. The two groups were analyzed for LOS, operation time, complications, visual analog scale (VAS), Oswestry Dysfunction Index (ODI), hospitalization expenses (HE), and improved MacNab efficacy assessment criteria (MacNab).

Results: A total of 120 single segment LDH patients (ERAS pathway 60 cases, traditional care pathway 60 cases) who were selected from January 2019 to January 2021 met the inclusion criteria. There was a significant difference in mean LOS postoperative VAS scores and ODI on the 3rd day after surgery between the two groups (P < 0.05). The incidence of complications and HE were similar in the two groups (P > 0.05). The mean LOS decreased from 3.47 ± 1.14 days to 5.65 ± 1.39 days after application of ERAS pathway (P < 0.05).

Conclusions: The ERAS pathway reduced LOS without resulting in additional complications after PETD. These findings support the application of the perioperative ERAS pathway in the treatment of single-level LDH with PETD.

Level Of Evidence: Level IV, therapeutic.
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http://dx.doi.org/10.1186/s13018-021-02606-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285793PMC
July 2021

Expression mode and prognostic value of FXYD family members in colon cancer.

Aging (Albany NY) 2021 Jul 15;13(undefined). Epub 2021 Jul 15.

Department of Radiation Oncology, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China.

The FXYD gene family comprises seven members that encode a class of small-membrane proteins characterized by an FXYD motif and interact with Na/K-ATPase. Until now, the expression patterns and prognostic roles of the FXYD family in colon cancer (CC) have not been systematically reported. Gene expression, methylation, clinicopathological features and the prognoses of CC patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression feature and prognostic values of FXYD members were identified. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism underlying the function of the FXYD family in CC. Tumor Immune Estimation Resource (TIMER) and CIBERSORT analysis were used to assess the correlations between FXYD family members and tumor immune infiltrating cells (TIICs). FXYD family members were differentially expressed in CC except for FXYD2. FXYD2, FXYD3 and FXYD4 were revealed as independent prognostic factors for recurrence, while FXYD3 and FXYD7 were identified as prognostic factors for survival according to univariate and multivariate analyses with Cox regression. GSEA revealed that FXYD family members were involved in complicated biological functions underlying cancer progression. TIMER and CIBERSORT analyses showed significant associations between FXYD family genes and TIICs. The present study comprehensively revealed the expression mode and prognostic value of FXYD members in CC, providing insights for further study of the FXYD family as potential clinical biomarkers in CC.
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http://dx.doi.org/10.18632/aging.203290DOI Listing
July 2021

Overexpression of replication protein A3 is associated with unfavorable outcome in bladder urothelial carcinoma.

J Cancer Res Ther 2021 Jul;17(3):771-776

Department of Radiotherapy, Shandong Second Provincial General Hospital (Shandong Provincial ENT Hospital), Jinan, Shandong, China.

Purpose: The replication protein A3 (RPA3) is a subunit of the RPA protein complex, which plays an essential role in multiple processes of DNA metabolism. However, the involvement of RPA3 bladder urothelial carcinoma (UC) prognosis has not yet been elucidated. The aim of our study is to investigate the prognostic role of RPA3 expression in patients with bladder UC.

Materials And Methods: Bladder UC tissue specimens from 155 consecutively treated patients who underwent surgery between 2013 and 2018 were evaluated. The RPA3 expression was determined by immunohistochemistry, Western blot, and correlated with clinicopathological parameters. The prognostic significance of RPA3 expression was explored using the univariate and multivariate survival analysis of 155 patients who were followed.

Results: A total of 155 tissue specimens "of patients" who were regularly followed with the mean 39.6 months (from 4 to 71 months). The expression of RPA3 was significantly associated with tumor grade (P = 0.031) and stage (P = 0.021), as well as tumor size (P = 0.034). In univariate analysis, RPA3 overexpression showed an unfavorable influence on recurrence-free survival with statistical significance (P < 0.01). TNM stage and grade also showed strong statistical relation with adverse recurrence-free survival (P < 0.01, P = 0.030). Multivariate analysis revealed that grade, stage, and RPA3 reactivity (P = 0.025, P < 0.01, P = 0.016) were identified as independent prognostic factors for recurrence-free survival in patients with bladder UC.

Conclusions: These results of this study proved that elevated expression of RPA3 was associated with worse clinical outcome in bladder UC patients. This finding suggested that RPA3 served as a potential prognostic biomarker, which could be useful to predict cancer evolution and may represent a novel therapeutic target for the intervention of bladder UC patients.
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http://dx.doi.org/10.4103/jcrt.jcrt_275_21DOI Listing
July 2021

Mobility speed predicts new-onset hypertension: a longitudinal study.

Blood Press Monit 2021 Jul 13. Epub 2021 Jul 13.

PT Department, College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences Department of Acupuncture, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Objective: The aim of this study was to investigate whether declining mobility and muscle strength predict new-onset hypertension in suburban-dwelling elderly individuals.

Methods: This study was designed as a longitudinal prospective cohort study. It was comprised of 362 individuals (mean age = 67.8 ± 6.2; 157 men) without hypertension at baseline. At baseline, all participants completed health questionnaires and underwent measurements of mobility [the Timed Up and Go test (TUGT) and 4-m walking test] and muscle strength (grip strength). At 1-year follow-up, we determined the number of participants who had developed new-onset hypertension. We then evaluated the relationship between above metrics and the development of hypertension.

Results: In the present study, 94 (26.0%) participants developed hypertension after 1 year. After adjusting for mixed factors, the TUGT scores [hazard ratio = 1.15; 95% confidence interval (CI), 1.10-1.31; P = 0.030] were positively associated with the development of hypertension, while the 4-m walking test scores (hazard ratio = 0.07; 95% CI, 0.01-0.47; P = 0.007) showed an inverse relationship with hypertension incidence. Grip strength (hazard ratio = 1.03; 95% CI, 0.99-1.06; P = 0.098) was not significantly associated with hypertension incidence.

Conclusion: Our results indicate that people with declining mobility are significantly more likely to develop hypertension. Hence, improving mobility could be protective against hypertension for elderly individuals.
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http://dx.doi.org/10.1097/MBP.0000000000000562DOI Listing
July 2021

Clubroot resistance derived from the European Brassica napus cv. 'Tosca' is not effective against virulent Plasmodiophora brassicae isolates from Alberta, Canada.

Sci Rep 2021 Jul 14;11(1):14472. Epub 2021 Jul 14.

Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada.

In this study, clubroot resistance in the resynthesized European winter Brassica napus cv. 'Tosca' was introgressed into a Canadian spring canola line '11SR0099', which was then crossed with the clubroot susceptible spring line '12DH0001' to produce F seeds. The F plants were used to develop a doubled haploid (DH) mapping population. The parents and the DH lines were screened against 'old' pathotypes 2F, 3H, 5I, 6M and 8N of the clubroot pathogen, Plasmodiophora brassicae, as well as against the 'new' pathotypes 5X, 5L, 2B, 3A, 3D, 5G, 8E, 5C, 8J, 5K, 3O and 8P. Genotyping was conducted using a Brassica 15K SNP array. The clubroot screening showed that 'Tosca, '11SR0099' and the resistant DH lines were resistant to three (2F, 3H and 5I) of the five 'old' pathotypes and four (2B, 3O, 8E and 8P) of the 12 'new' pathotypes, while being moderately resistant to the 'old' pathotype 8N and the 'new' pathotypes 3D and 5G. 'Tosca' was susceptible to isolates representing pathotype 3A (the most common among the 'new' pathotypes) as well as pathotypes 6M, 5X, 5L, 5K and 8J. Linkage analysis and QTL mapping identified a ca. 0.88-0.95 Mb genomic region on the A03 chromosome of 'Tosca' as conferring resistance to pathotypes 2F, 3H, 5I, 2B, 3D, 5G, 8E, 3O and 8P. The identified QTL genomic region housed the CRk, Crr3 and CRd gene(s). However, the susceptibility of 'Tosca' to most of the common virulent pathotypes makes it unattractive as a sole CR donor in the breeding of commercial canola varieties in western Canada.
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http://dx.doi.org/10.1038/s41598-021-93327-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280172PMC
July 2021

Implication of long non-coding RNA NEAT1 in the pathogenesis of bacterial meningitis-induced blood-brain barrier damage.

Microvasc Res 2021 Jul 10:104225. Epub 2021 Jul 10.

Department of Pharmacy, The First Hospital of Qiqihar, Qiqihar 161000, PR China.

Purpose: Blood-brain barrier (BBB) damage is closely related to various neurological disorders, including bacterial meningitis (BM). Determining a reliable strategy to prevent BBB damage in the context of infection would be highly desirable. In the present study, we investigated the implications of the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in moderating BBB damage.

Methods: In vitro BBB models were developed by co-culturing hCMEC/D3 cells with glioma cells, whereupon the glioma-exposed endothelial cells (GECs) were treated with a series of mimics, inhibitors, overexpression plasmids, and shRNAs for evaluating whether NEAT1, microRNA-135a (miR-135a) and hypoxia-inducible factor 1α (HIF1α) mediated BBB integrity and permeability. Furthermore, the in vivo biological function of NEAT1 was validated in a mouse model of BBB damage.

Results: NEAT1 and HIF1α were determined to be up-regulated, while miR-135a was under-expressed in GECs. As demonstrated by chromatin immunoprecipitation and dual-luciferase reporter assays, NEAT1 could bind to miR-135a, and HIF1α was confirmed as a target of miR-135a. Either overexpression of NEAT1 or depletion of miR-135a impaired the integrity and augmented the permeability of BBB. However, HIF1α silencing could reverse the BBB damage induced by NEAT1 overexpression or by inhibition of miR-135a. In vivo experiments substantiated that knockdown of NEAT1 could alleviate BBB damage in living mice.

Conclusions: Hence, NEAT1 knockdown prevents BBB disruption and exerts promise as a potential target for BM treatment.
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http://dx.doi.org/10.1016/j.mvr.2021.104225DOI Listing
July 2021

Enantioselective Synthesis of Fused Isocoumarins via Palladium-Catalyzed Annulation of Alkyne-Tethered Malononitriles.

J Org Chem 2021 Jul 13. Epub 2021 Jul 13.

Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), and College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China.

An enantioselective palladium-catalyzed annulation of alkyne-tethered malononitriles for the synthesis of 3,4-ring-fused isocoumarins is described. This cascade strategy involves oxypalladation of -alkynylbenzoates and desymmetrizing addition onto one cyano group of the pendant malononitriles, which enables the concurrent construction of two rings and an all-carbon quaternary stereocenter in a single operation.
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http://dx.doi.org/10.1021/acs.joc.1c01026DOI Listing
July 2021

Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny.

Gut 2021 Jul 12. Epub 2021 Jul 12.

Department of Hepatobiliary and Pancreatic Surgery, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, China

Objective: Hepatocellular carcinoma (HCC) tumour microenvironment (TME) is highly complex with diverse cellular components organising into various functional units, cellular neighbourhoods (CNs). And we wanted to define CN of HCC while preserving the TME architecture, based on which, potential targets for novel immunotherapy could be identified.

Design: A highly multiplexed imaging mass cytometry (IMC) panel was designed to simultaneously quantify 36 biomarkers of tissues from 134 patients with HCC and 7 healthy donors to generate 562 highly multiplexed histology images at single-cell resolution. Different function units were defined by topological analysis of TME. CN relevant to the patients' prognosis was identified as specific target for HCC therapy. Transgenic mouse models were used to validate the novel immunotherapy target for HCC.

Results: Three major types of intratumour areas with distinct distribution patterns of tumorous, stromal and immune cells were identified. 22 cellular metaclusters and 16 CN were defined. CN composed of various types of cells formed regional function units and the regional immunity was regulated reversely by resident Kupffer cells and infiltrating macrophages with protumour and antitumour function, respectively. Depletion of Kupffer cells in mouse liver largely enhances the T cell response, reduces liver tumour growth and sensitises the tumour response to antiprogrammed cell death protein-1 treatment.

Conclusion: Our findings reveal for the first time the various topological function units of HCC TME, which also presents the largest depository of pathological landscape for HCC. This work highlights the potential of Kupffer cell-specific targeting rather than overall myeloid cell blocking as a novel immunotherapy for HCC treatment.
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http://dx.doi.org/10.1136/gutjnl-2021-324339DOI Listing
July 2021

High-quality genome assembly of Huazhan and Tianfeng, the parents of an elite rice hybrid Tian-you-hua-zhan.

Sci China Life Sci 2021 Jun 28. Epub 2021 Jun 28.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.

High-quality rice reference genomes have accelerated the comprehensive identification of genome-wide variations and research on functional genomics and breeding. Tian-you-hua-zhan has been a leading hybrid in China over the past decade. Here, de novo genome assembly strategy optimization for the rice indica lines Huazhan (HZ) and Tianfeng (TF), including sequencing platforms, assembly pipelines and sequence depth, was carried out. The PacBio and Nanopore platforms for long-read sequencing were utilized, with the Canu, wtdbg2, SMARTdenovo, Flye, Canu-wtdbg2, Canu-SMARTdenovo and Canu-Flye assemblers. The combination of PacBio and Canu was optimal, considering the contig N50 length, contig number, assembled genome size and polishing process. The assembled contigs were scaffolded with Hi-C data, resulting in two "golden quality" rice reference genomes, and evaluated using the scaffold N50, BUSCO, and LTR assembly index. Furthermore, 42,625 and 41,815 non-transposable element genes were annotated for HZ and TF, respectively. Based on our assembly of HZ and TF, as well as Zhenshan97, Minghui63, Shuhui498 and 9311, comprehensive variations were identified using Nipponbare as a reference. The de novo assembly strategy for rice we optimized and the "golden quality" rice genomes we produced for HZ and TF will benefit rice genomics and breeding research, especially with respect to uncovering the genomic basis of the elite traits of HZ and TF.
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http://dx.doi.org/10.1007/s11427-020-1940-9DOI Listing
June 2021

The immunoenhancement effects of sea buckthorn pulp oil in cyclophosphamide-induced immunosuppressed mice.

Food Funct 2021 Jul 12. Epub 2021 Jul 12.

Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou, 313000, China.

In this study, the immunomodulatory effect of sea buckthorn (SBT) pulp oil was elucidated in immunosuppressed Balb/c mice induced by cyclophosphamide (CTX). The results showed that SBT pulp oil could reverse the decreasing trend of body weight, thymus/spleen index and hematological parameters induced by CTX. Compared with immunosuppressive mice induced by CTX, SBT pulp oil could enhance NK cytotoxicity, macrophage phagocytosis, and T lymphocyte proliferation, and regulate the proportion of T cell subsets in mesenteric lymph nodes (MLN), and promote the production of secretory immunoglobulin A (sIgA), IFN-γ, IL-2, IL-4, IL-12 and TNF-α in the intestines. In addition, SBT pulp oil can promote the production of short fatty acids (SCFAs), increase the diversity of gut microbiota, improve the composition of intestinal flora, increase the abundance of Alistipes, Bacteroides, Anaerotruncus, Lactobacillus, ASF356, and Roseburia, while decreasing the abundance of Mucispirillum, Anaeroplasma, Pelagibacterium, Brevundimonas, Ochrobactrum, Acinetobacter, Ruminiclostridium, Blautia, Ruminiclostridium, Oscillibacter, and Faecalibaculum. This study shows that SBT pulp oil can regulate the diversity and composition of intestinal microflora in CTX-induced immunosuppressive Balb/c mice, thus enhancing the intestinal mucosa and systemic immune response. The results can provide a basis for understanding the function of SBT pulp oil and its application as a new probiotic and immunomodulator.
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http://dx.doi.org/10.1039/d1fo01257fDOI Listing
July 2021

Induction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases.

Wellcome Open Res 2021 23;6:52. Epub 2021 Jun 23.

Department of Developmental and Molecular Biology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, 10461, USA.

Metastatic breast cancer cells recruit macrophages (metastasis-associated macrophages, or MAMs) to facilitate their seeding, survival and outgrowth. However, a comprehensive understanding of the gene expression program in MAMs and how this program contributes to metastasis remain elusive. We compared the transcriptomes of MAMs recruited to lung metastases and resident alveolar macrophages (RAMs) and identified a large variety of differentially expressed genes and their associated signaling pathways. Some of the changes were validated using qRT-PCR and immunofluorescence. To probe the functional relevance to metastatic growth, a gene-targeting mouse model of female mice in the C57BL6/J background was used to study allograft inflammatory factor 1 (AIF1, also known as ionized calcium-binding adapter molecule 1 or IBA1). Interferon signaling is one of the most activated pathways in MAMs, with strong upregulation of multiple components of the pathway and a significant enrichment for the gene signatures of interferon-alpha-treated human macrophages. , an interferon-responsive gene that regulates multiple macrophage activities, was robustly induced in MAMs. deficiency in MAMs, however, did not affect development of lung metastases, suggesting that AIF1 indicates MAM activation but is dispensable for regulating metastasis. The drastically different gene expression profile of MAMs as compared to RAMs suggests an important role in promoting metastatic growth. Dissection of the underlying mechanisms and functional validation of potential targets in the profile may provide novel therapeutic strategies for the treatment of metastatic diseases.
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http://dx.doi.org/10.12688/wellcomeopenres.16569.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008350.2PMC
June 2021

Protein disulfide isomerase inhibits endoplasmic reticulum stress response and apoptosis via its oxidoreductase activity in colorectal cancer.

Cell Signal 2021 Jul 7;86:110076. Epub 2021 Jul 7.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address:

Protein disulfide isomerase (PDI), a principal endoplasmic reticulum resident oxidoreductase chaperone, is known to play a role in malignancies. This study aims to explore the molecular mechanism by which PDI regulates endoplasmic reticulum stress and the apoptosis signaling pathway in colorectal cancer (CRC). We determined the expression of PDI in CRC tissues and adjacent normal tissues. Gain- and loss- of function assays were conducted to evaluate the effects of PDI on oxidative stress, endoplasmic reticulum stress, and apoptosis in CRC cells, as reflected by hydrogen peroxide (HO) level and the expression of related proteins. PDI protein expression was upregulated in CRC tissues. Small molecule inhibitor of PDI or PDI knockdown reduced CRC cell viability and induced apoptosis. Overexpression of wild-type PDI augmented the viability of CRC cells and inhibited endoplasmic reticulum stress response and apoptosis. Small molecule inhibitor of PDI or PDI knockdown increased intracellular HO level and activated apoptosis signaling pathway, which could be reversed by wild-type PDI restoration. Moreover, the catalytic active site of C-terminal of PDI was found to be indispensable for the regulatory effects of PDI on HO levels, apoptosis and cell viability in CRC cells. Collectively, PDI inhibits endoplasmic reticulum stress and apoptosis of CRC cells through its oxidoreductase activity, thereby promoting the malignancy of CRC.
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http://dx.doi.org/10.1016/j.cellsig.2021.110076DOI Listing
July 2021

Up-Scalable Fabrication of SnO with Multifunctional Interface for High Performance Perovskite Solar Modules.

Nanomicro Lett 2021 Jul 10;13(1):155. Epub 2021 Jul 10.

Energy Materials and Surface Sciences Unit (EMSSU), Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa, 904-0495, Japan.

Tin dioxide (SnO) has been demonstrated as one of the promising electron transport layers for high-efficiency perovskite solar cells (PSCs). However, scalable fabrication of SnO films with uniform coverage, desirable thickness and a low defect density in perovskite solar modules (PSMs) is still challenging. Here, we report preparation of high-quality large-area SnO films by chemical bath deposition (CBD) with the addition of KMnO. The strong oxidizing nature of KMnO promotes the conversion from Sn(II) to Sn(VI), leading to reduced trap defects and a higher carrier mobility of SnO. In addition, K ions diffuse into the perovskite film resulting in larger grain sizes, passivated grain boundaries, and reduced hysteresis of PSCs. Furthermore, Mn ion doping improves both the crystallinity and the phase stability of the perovskite film. Such a multifunctional interface engineering strategy enabled us to achieve a power conversion efficiency (PCE) of 21.70% with less hysteresis for lab-scale PSCs. Using this method, we also fabricated 5 × 5 and 10 × 10 cm PSMs, which showed PCEs of 15.62% and 11.80% (active area PCEs are 17.26% and 13.72%), respectively. For the encapsulated 5 × 5 cm PSM, we obtained a T operation lifetime (the lifespan during which the solar module PCE drops to 80% of its initial value) exceeding 1000 h in ambient condition.
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http://dx.doi.org/10.1007/s40820-021-00675-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271052PMC
July 2021

Mediating effects of lower extremity function on the relationship between night sleep duration and cardiovascular disease risk: a cross-sectional study in elderly Chinese without cardiovascular diseases.

BMJ Open 2021 Jul 8;11(7):e046015. Epub 2021 Jul 8.

Shanghai University of Traditional Chinese Medicine, Shanghai, China

Objective: The purpose of this study is to investigate the mediating effect of physical performance on the relationship between night sleep duration and risk of cardiovascular disease (CVD) in elderly Chinese without CVD.

Methods: 782 participants without CVD over 65 years (average: 70.82±3.86 years, 448 women) were included in this study. CVD risk was calculated by the Framingham Risk Score and participants were divided into four groups of night sleep duration (in hours): <7 hours, ≥7-8 hours, >8-9 hours and >9 hours. Upper extremity function was measured by grip strength and lower extremity function was measured by the Short Physical Performance Battery (SPPB), consisting of balance, 4 m walk and chair stands tests.

Results: After adjusting for covariates, long night sleep duration (>9 hours) and CVD risk were significantly positively associated compared with moderate night sleep duration (≥7-8 hours) (β=1.152; 95% CI 0.05 to 2.25). SPPB total score (indirect effect ab=-0.122; 95% CI -0.291 to -0.0008) rather than grip strength partially mediated the relationship between long night sleep duration and CVD risk, in which chair stands played a major mediating role (indirect effect ab=-0.171; 95% CI -0.040 to -0.0006), while balance (indirect effect ab=-0.016; 95% CI -0.100 to 0.063) and 4 m walk (indirect effect ab=0.048; 95% CI -0.066 to 0.201) did not.

Conclusions: Lower extremity function, especially lower limb muscle strength, partially mediates a positive association between long night sleep duration and CVD risk in the elderly without CVD. Suitable interventions for physical performance and sleep may minimise the risk of subsequent CVD.
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http://dx.doi.org/10.1136/bmjopen-2020-046015DOI Listing
July 2021

An MST4-pβ-Catenin Signaling Axis Controls Intestinal Stem Cell and Tumorigenesis.

Adv Sci (Weinh) 2021 Jul 8:e2004850. Epub 2021 Jul 8.

State Key Laboratory of Genetic Engineering, Department of Cell and Developmental Biology, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.

Elevated Wnt/β-catenin signaling has been commonly associated with tumorigenesis especially colorectal cancer (CRC). Here, an MST4-pβ-catenin signaling axis essential for intestinal stem cell (ISC) homeostasis and CRC development is uncovered. In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates β-catenin at Thr40 to block its Ser33 phosphorylation by GSK3β. Thus, MST4 mediates an active process that prevents β-catenin from binding to and being degraded by β-TrCP, leading to accumulation and full activation of β-catenin. Depletion of MST4 causes loss of ISCs and inhibits CRC growth. Mice bearing either MST4 mutation with constitutive kinase activity or β-catenin mutation mimicking MST4-mediated phosphorylation show overly increased ISCs/CSCs and exacerbates CRC. Furthermore, the MST4-pβ-catenin axis is upregulated and correlated with poor prognosis of human CRC. Collectively, this work establishes a previously undefined machinery for β-catenin activation, and further reveals its function in stem cell and tumor biology, opening new opportunities for targeted therapy of CRC.
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http://dx.doi.org/10.1002/advs.202004850DOI Listing
July 2021