Publications by authors named "Long Zhang"

1,169 Publications

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Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation.

Cell Rep 2021 Sep;36(12):109740

Department of Pharmacology, Zhejiang University City College, Hangzhou 310015, China. Electronic address:

Bub1 is required for the kinetochore/centromere localization of two essential mitotic kinases Plk1 and Aurora B. Surprisingly, stable depletion of Bub1 by ∼95% in human cells marginally affects whole chromosome segregation fidelity. We show that CENP-U, which is recruited to kinetochores by the CENP-P and CENP-Q subunits of the CENP-O complex, is required to prevent chromosome mis-segregation in Bub1-depleted cells. Mechanistically, Bub1 and CENP-U redundantly recruit Plk1 to kinetochores to stabilize kinetochore-microtubule attachments, thereby ensuring accurate chromosome segregation. Furthermore, unlike its budding yeast homolog, the CENP-O complex does not regulate centromeric localization of Aurora B. Consistently, depletion of Bub1 or CENP-U sensitizes cells to the inhibition of Plk1 but not Aurora B kinase activity. Taken together, our findings provide mechanistic insight into the regulation of kinetochore function, which may have implications for targeted treatment of cancer cells with mutations perturbing kinetochore recruitment of Plk1 by Bub1 or the CENP-O complex.
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http://dx.doi.org/10.1016/j.celrep.2021.109740DOI Listing
September 2021

Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells.

Proc Natl Acad Sci U S A 2021 Sep;118(39)

Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;

Tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) are caused by aberrant mechanistic Target of Rapamycin Complex 1 (mTORC1) activation due to loss of either or Cytokine profiling of TSC2-deficient LAM patient-derived cells revealed striking up-regulation of Interleukin-6 (IL-6). LAM patient plasma contained increased circulating IL-6 compared with healthy controls, and TSC2-deficient cells showed up-regulation of IL-6 transcription and secretion compared to wild-type cells. IL-6 blockade repressed the proliferation and migration of TSC2-deficient cells and reduced oxygen consumption and extracellular acidification. U-C glucose tracing revealed that IL-6 knockout reduced 3-phosphoserine and serine production in TSC2-deficient cells, implicating IL-6 in de novo serine metabolism. IL-6 knockout reduced expression of phosphoserine aminotransferase 1 (PSAT1), an essential enzyme in serine biosynthesis. Importantly, recombinant IL-6 treatment rescued PSAT1 expression in the TSC2-deficient, IL-6 knockout clones selectively and had no effect on wild-type cells. Treatment with anti-IL-6 (αIL-6) antibody similarly reduced cell proliferation and migration and reduced renal tumors in mice while reducing PSAT1 expression. These data reveal a mechanism through which IL-6 regulates serine biosynthesis, with potential relevance to the therapy of tumors with mTORC1 hyperactivity.
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http://dx.doi.org/10.1073/pnas.2101268118DOI Listing
September 2021

A synergistic consortium involved in -dichlorprop degradation as revealed by DNA-stable isotope probing and metagenomics analysis.

Appl Environ Microbiol 2021 Sep 15:AEM0156221. Epub 2021 Sep 15.

Department of Microbiology, Key Lab of Microbiology for Agricultural Environment, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, 210095, Nanjing, China.

-dichlorprop, a commonly used phenoxyalkanoic acid herbicide, is frequently detected in environments and poses threats to environmental safety and human health. Microbial consortia are thought to play key roles in -dichlorprop degradation. However, the compositions of the microbial consortia involved in -dichlorprop degradation remain largely unknown. In this study, DNA-stable isotope probing and metagenomics analysis were integrated to reveal the key microbial consortium responsible for -dichlorprop degradation in a -dichlorprop-degrading enrichment. OTU340 ( sp.) and OTU348 ( sp.) were significantly enriched in the C--dichlorprop-labeled heavy DNA fractions. A -dichlorprop degrader, sp. L3, was isolated from the enrichment by traditional enrichment method but with additional supplementation of the antibiotic ciprofloxacin, which was instructed by metagenomics analysis of the associations between -dichlorprop-degraders and antibiotic resistance genes. As revealed by functional profiling of the metagenomes of the heavy DNA, the genes and , involved in the initial degradation of the ()- and ()-enantiomers of dichlorprop respectively, were mostly taxonomically assigned to species, indicating that species might harbor novel dichlorprop degrading genes. In addition, taxonomically diverse bacterial genera such as , , , and were presumed to synergistically cooperate with the key degraders for enhanced degradation of -dichlorprop. Understanding of the key microbial consortium involved in the degradation of the phenoxyalkanoic acid herbicide of -dichlorprop is pivotal for design of synergistic consortia used for enhanced bioremediation of herbicide-contaminated sites. However, the composition of microbial consortium and the interactions between community members during the biodegradation of -dichlorprop are unclear. In this study, DNA-SIP and metagenomics analysis were integrated to reveal that the metabolite 2,4-dichlorophenol degraders , , , and synergistically cooperated with the key degraders / for enhanced degradation of -dichlorprop. Our study provides new insights into the synergistic degradation of -dichlorprop at the community level and implies the existence of novel degrading genes for -dichlorprop in nature.
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http://dx.doi.org/10.1128/AEM.01562-21DOI Listing
September 2021

Follow-up study on the COVID-19 survivors after one year discharged from hospital.

Int J Infect Dis 2021 Sep 11. Epub 2021 Sep 11.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450051, China. Electronic address:

Objective: To evaluate the long-term consequences of survivors with COVID-19 one year after recovery, and to identify the risk factors associated with abnormal patterns in chest imaging manifestations, or impaired lung function.

Methods: COVID-19 patients were recruited and prospectively followed up with symptoms, HRQoL (health-related quality of life), psychological questionnaires, 6MWT (6-minute walking test), chest CT, PFTs and blood tests. Multivariable logistic regression models were used to evaluate the association between the clinical characteristics and the chest CT abnormalities or the pulmonary function.

Results: Ninety-four patients with COVID-19 were recruited between January 16 and February 6, 2021. Muscle fatigue and insomnia were the most common symptoms. Chest CT scan were abnormal in 71.28% of participants. Results of multivariable regression showed an increase odd in age. Ten patients had impairment of DLCO (diffusing capacity of the lung for carbon monoxide). Urea nitrogen concentration on admission was significantly associated with impaired DLCO. The level of IgG and the neutralizing activity were significantly lower compared with those at the early phase.

Conclusions: One year after hospitalization for COVID-19, a cohort of survivors were mainly troubled with muscle fatigue and insomnia. Pulmonary structural abnormalities and pulmonary diffusion capacities were highly prevalent in surviving COVID-19 patients. It is necessary to intervene main target population for long-term recovery.
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http://dx.doi.org/10.1016/j.ijid.2021.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434916PMC
September 2021

PCage: Fluorescent Molecular Temples for Binding Sugars in Water.

J Am Chem Soc 2021 Sep 10. Epub 2021 Sep 10.

Department of Chemistry, 2145 Sheridan Road, Northwestern University, Evanston, Illinois 60208, United States.

The development of synthetic receptors that recognize carbohydrates in water with high selectivity and specificity is challenging on account of their structural complexity and strong hydrophilicity. Here, we report on the design and synthesis of two pyrene-based, temple-shaped receptors for the recognition of a range of common sugars in water. These receptors rely on the use of two parallel pyrene panels, which serve as roofs and floors, capable of forming multiple [C-H···π] interactions with the axially oriented C-H bonds on glycopyranosyl rings in the carbohydrate-based substrates. In addition, eight polarized pyridinium C-H bonds, projecting from the roofs and floors of the temple receptors toward the binding cavities, form [C-H···O] hydrogen bonds, with the equatorially oriented OH groups on the sugars located inside the hydrophobic cavities. Four -xylylene pillars play a crucial role in controlling the distance between the roof and floor. These temple receptors are highly selective for the binding of glucose and its derivatives. Furthermore, they show enhanced fluorescence upon binding with glucose in water, a property which is useful for glucose-sensing in aqueous solution.
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http://dx.doi.org/10.1021/jacs.1c06333DOI Listing
September 2021

Correction to: Occurrence and Prognostic Value of Perineural Invasion in Esophageal Squamous Cell Cancer: A Retrospective Study.

Ann Surg Oncol 2021 Sep 9. Epub 2021 Sep 9.

Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.1245/s10434-021-10760-1DOI Listing
September 2021

Corrigendum: Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies.

Front Oncol 2021 17;11:745052. Epub 2021 Aug 17.

Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Department of Rare and Head and Neck Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.

[This corrects the article DOI: 10.3389/fonc.2021.658552.].
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http://dx.doi.org/10.3389/fonc.2021.745052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416238PMC
August 2021

[F]PBR146 and [F]DPA-714 Imaging of Neuroinflammation in Chronic Hepatic Encephalopathy Rats.

Front Neurosci 2021 16;15:678144. Epub 2021 Aug 16.

Department of Diagnostic Radiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Neuroinflammation is an important pathogenesis of hepatic encephalopathy (HE). The upregulation of translocator protein (TSPO) during neuroinflammation provides an imaging molecular target to evaluate the severity of neuroinflammation in chronic HE rats. [18F]DPA-714 and [18F]PBR146 targeting TSPO are often used for neuroinflammation imaging. This study performed bile duct ligation (BDL) in rats to simulate chronic HE model, tested the behavioral experiments, and conducted [18F]PBR146 and [18F]DPA-714 micro-PET/CT scans followed analyzing the average %ID/g values of the whole brain, brain regions and main organs of subjects. After sacrifice the rats, the blood plasma samples were taken for blood biochemical indexes and plasma inflammatory factor levels examination, the liver and brain specimens were obtained for pathological analysis. The BDL rats showed chronic liver failure with defects in cognition, motor coordination ability and mental state. [18F]PBR146 and [18F]DPA-714 micro-PET/CT imaging results were similar in whole brain of BDL group and Sham group. Besides, some regional brain areas in BDL rats were found abnormal uptakes mainly located in basal ganglia area, auditory cortex, motor cortex, cingulate gyrus, somatosensory cortex, hippocampus, thalamus, midbrain, and medulla oblongata, and these regions also correlated with behavioral alterations. In conclusion, both [18F]PBR146 and [18F]DPA-714 had the similar imaging effects in hepatic encephalopathy models could quantitatively evaluate neuroinflammation load and distribution. The difference brain regions with higher uptake values of radiotracers in BDL rats were correlated with behavioral alterations.
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http://dx.doi.org/10.3389/fnins.2021.678144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415356PMC
August 2021

ASO Visual Abstract: Occurrence and Prognostic Value of Perineural Invasion in Esophageal Squamous Cell Cancer: A Retrospective Study.

Ann Surg Oncol 2021 Sep 3. Epub 2021 Sep 3.

Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Rd., Shanghai, 200030, China.

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http://dx.doi.org/10.1245/s10434-021-10741-4DOI Listing
September 2021

Harvesting High-Quality White-Light Emitting and Remarkable Emission Enhancement in One-Dimensional Halide Perovskites Upon Compression.

JACS Au 2021 Apr 2;1(4):459-466. Epub 2021 Mar 2.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun 130012, China.

The pressure induced emission (PIE) behavior of halide perovskites has attracted extensive interest due to its potential application in pressure sensors and trademark security. However, the PIE phenomenon of white-light-emitting hybrid perovskites (WHPs) is rare, and that at pressures above 10.0 GPa has never been reported. Here, we effectively adjusted the perovskite to emit high-quality "cold" or "warm" white light and successfully realized pressure-induced emission (PIE) upon even higher pressure up to 35.1 GPa in one-dimensional halide perovskite CNHPbCl. We reveal that the degree of structural distortion and the rearrangement of the multiple self-trapped states position are consistent with the intriguing photoluminescence variation, which is further supported by high-pressure synchrotron X-ray diffraction experiments and time-resolved photoluminescence decay dynamics data. The underlying relationship between octahedron behavior and emission plays a key role to obtain high-quality white emission perovskites. We anticipate that this work enhances our understanding of structure-dependent self-trapped exciton (STE) emission characteristics and stimulates the design of high-performance WHPs for next generation white LED lighting devices.
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http://dx.doi.org/10.1021/jacsau.1c00024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395689PMC
April 2021

A contorted nanographene shelter.

Nat Commun 2021 08 31;12(1):5191. Epub 2021 Aug 31.

Department of Chemistry, Northwestern University, Evanston, IL, USA.

Nanographenes have kindled considerable interest in the fields of materials science and supramolecular chemistry as a result of their unique self-assembling and optoelectronic properties. Encapsulating the contorted nanographenes inside artificial receptors, however, remains challenging. Herein, we report the design and synthesis of a trigonal prismatic hexacationic cage, which has a large cavity and adopts a relatively flexible conformation. It serves as a receptor, not only for planar coronene, but also for contorted nanographene derivatives with diameters of approximately 15 Å and thicknesses of 7 Å. A comprehensive investigation of the host-guest interactions in the solid, solution and gaseous states by experimentation and theoretical calculations reveals collectively an induced-fit binding mechanism with high binding affinities between the cage and the nanographenes. Notably, the photostability of the nanographenes is improved significantly by the ultrafast deactivation of their excited states within the cage. Encapsulating the contorted nanographenes inside the cage provides a noncovalent strategy for regulating their photoreactivity.
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http://dx.doi.org/10.1038/s41467-021-25255-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408160PMC
August 2021

Toward On-Device Federated Learning: A Direct Acyclic Graph-Based Blockchain Approach.

IEEE Trans Neural Netw Learn Syst 2021 Aug 30;PP. Epub 2021 Aug 30.

Due to the distributed characteristics of federated learning (FL), the vulnerability of the global model and the coordination of devices are the main obstacle. As a promising solution of decentralization, scalability, and security, leveraging the blockchain in FL has attracted much attention in recent years. However, the traditional consensus mechanisms designed for blockchain-like proof of work (PoW) would cause extreme resource consumption, which reduces the efficiency of FL greatly, especially when the participating devices are wireless and resource-limited. In order to address device asynchrony and anomaly detection in FL while avoiding the extra resource consumption caused by blockchain, this article introduces a framework for empowering FL using direct acyclic graph (DAG)-based blockchain systematically (DAG-FL). Accordingly, DAG-FL is first introduced from a three-layer architecture in detail, and then, two algorithms DAG-FL Controlling and DAG-FL Updating are designed running on different nodes to elaborate the operation of the DAG-FL consensus mechanism. After that, a Poisson process model is formulated to discuss that how to set deployment parameters to maintain DAG-FL stably in different FL tasks. The extensive simulations and experiments show that DAG-FL can achieve better performance in terms of training efficiency and model accuracy compared with the typical existing on-device FL systems as the benchmarks.
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http://dx.doi.org/10.1109/TNNLS.2021.3105810DOI Listing
August 2021

Scale Drop Disease Virus Associated Yellowfin Seabream () Ascites Diseases, Zhuhai, Guangdong, Southern China: The First Description.

Viruses 2021 Aug 16;13(8). Epub 2021 Aug 16.

Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, China.

Scale drop disease virus (SDDV), an emerging piscine iridovirus prevalent in farmed Asian seabass in Southeast Asia, was firstly scientifically descripted in Singapore in 2015. Here, an SDDV isolate ZH-06/20 was isolated by inoculating filtered ascites from diseased juvenile yellowfin seabream into MFF-1 cell. Advanced cytopathic effects were observed 6 days post-inoculation. A transmission electron microscopy examination confirmed that numerous virion particles, about 140 nm in diameter, were observed in infected MFF-1 cell. ZH-06/20 was further purified and both whole genome and virion proteome were determined. The results showed that ZH-06/20 was composed of 131,122 bp with 135 putative viral proteins and 113 of them were further detected by virion proteome. Western blot analysis showed that no (or weak) cross-reaction was observed among several major viral proteins between ZH-06/20 and ISKNV-like megalocytivirus. An artificial challenge showed that ZH-06/20 could cause 100% death to juvenile yellowfin seabream. A typical sign was characterized by severe ascites, but not scale drop, which was considerably different from SDD syndrome in Asian seabass. Collectively, SDDV was confirmed, for the first time, as the causative agent of ascites diseases in farmed yellowfin seabream. Our study offers useful information to better understanding SDDV-associated diseases in farmed fish.
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http://dx.doi.org/10.3390/v13081617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402775PMC
August 2021

Quantum Dot Self-Assembly Enables Low-Threshold Lasing.

Adv Sci (Weinh) 2021 Aug 27:e2101125. Epub 2021 Aug 27.

The Edward S. Rogers Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Road, Toronto, Ontario, M5S 3G4, Canada.

Perovskite quantum dots (QDs) are of interest for solution-processed lasers; however, their short Auger lifetime has limited lasing operation principally to the femtosecond temporal regime the photoexcitation levels to achieve optical gain threshold are up to two orders of magnitude higher in the nanosecond regime than in the femtosecond. Here the authors report QD superlattices in which the gain medium facilitates excitonic delocalization to decrease Auger recombination and in which the macroscopic dimensions of the structures provide the optical feedback required for lasing. The authors develope a self-assembly strategy that relies on sodiumd-an assembly director that passivates the surface of the QDs and induces self-assembly to form ordered three-dimensional cubic structures. A density functional theory model that accounts for the attraction forces between QDs allows to explain self-assembly and superlattice formation. Compared to conventional organic-ligand-passivated QDs, sodium enables higher attractive forces, ultimately leading to the formation of micron-length scale structures and the optical faceting required for feedback. Simultaneously, the decreased inter-dot distance enabled by the new ligand enhances exciton delocalization among QDs, as demonstrated by the dynamically red-shifted photoluminescence. These structures function as the lasing cavity and the gain medium, enabling nanosecond-sustained lasing with a threshold of 25 µJ cm .
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http://dx.doi.org/10.1002/advs.202101125DOI Listing
August 2021

Follistatin-controlled activin-HNF4α-coagulation factor axis in liver progenitor cells determines outcome of acute liver failure.

Hepatology 2021 Aug 26. Epub 2021 Aug 26.

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Background & Aims: In patients with acute liver failure (ALF) who suffer from massive hepatocyte loss, liver progenitor cells (LPC) take over key hepatocyte functions, which ultimately determines survival. This study investigated how the expression of HNF4α, its regulators and targets in LPC determines clinical outcome of ALF patients.

Approach & Results: Clinicopathological associations were scrutinized in 19 ALF patients (9 recovered and 10 receiving liver transplantation). Regulatory mechanisms between follistatin, activin, HNF4α and coagulation factor expression in LPC were investigated in vitro and in metronidazole-treated zebrafish. A prospective clinical study followed up 186 cirrhotic patients for 80 months to observe the relevance of follistatin levels in prevalence and mortality of acute-on-chronic liver failure (ACLF). Recovered ALF patients robustly express HNF4α in either LPC or remaining hepatocytes. As in hepatocytes, HNF4α controls the expression of coagulation factors by binding to their promoters in LPC. HNF4α expression in LPC requires the FOXH1-SMAD2/3/4 transcription factor complex, which is promoted by the TGF-β superfamily member activin. Activin signaling in LPC is negatively regulated by follistatin, a hepatocyte-derived hormone controlled by insulin and glucagon. In contrast to patients requiring liver transplantation, recovered patients demonstrate a normal activin/follistatin ratio, robust abundance of the activin effectors phosphorylated SMAD2 and HNF4α in LPC, leading to significantly improved coagulation function. A follow-up study indicated that serum follistatin levels could predict the incidence and mortality of ACLF.

Conclusions: These results highlight a crucial role of the follistatin-controlled activin-HNF4α-coagulation axis in determining the clinical outcome of massive hepatocyte loss-induced ALF. The effects of insulin and glucagon on follistatin suggests a key role of the systemic metabolic state in ALF.
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http://dx.doi.org/10.1002/hep.32119DOI Listing
August 2021

Occurrence and Prognostic Value of Perineural Invasion in Esophageal Squamous Cell Cancer: A Retrospective Study.

Ann Surg Oncol 2021 Aug 23. Epub 2021 Aug 23.

Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Objective: The aim of this study was to explore the occurrence and prognostic value of perineural invasion (PNI) as a classic tumor pathological feature in esophageal squamous cell carcinoma (ESCC).

Methods: We retrospectively enrolled 794 ESCC patients who underwent radical esophagectomy at Shanghai Chest Hospital from 2017 to 2018. The incidence, associated factors, and prognosis of PNI were analyzed.

Results: PNI was identified in 15.7% (125/794) of patients. The presence of PNI was significantly associated with depth of invasion (p < 0.001), pN stage (p = 0.008), tumor stage (p < 0.001), and lymphovascular invasion (LVI; p < 0.001). Multivariate logistic regression analysis demonstrated that advanced pT stage and LVI were independently associated with the presence of PNI, while multivariate Cox regression analysis demonstrated that PNI was not an independent risk factor for poor overall survival (OS) or recurrence-free survival (RFS) in ESCC patients (OS hazard ratio [HR] 0.688, 95% confidence interval [CI] 0.448-1.056, p = 0.087; RFS HR 0.837, 95% CI 0.551-1.273, p = 0.406). In the PNI-positive patient subgroup, adjuvant therapy was associated with better OS and RFS.

Conclusion: PNI correlates with, and may be a concomitant consequence of, LVI and advanced tumor invasion (T3-4) in ESCC patients. Although PNI was not identified as an independent prognostic indicator, our results suggest ESCC patients with PNI should be considered for adjuvant therapy.
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http://dx.doi.org/10.1245/s10434-021-10665-zDOI Listing
August 2021

TDO2 Was Downregulated in Hepatocellular Carcinoma and Inhibited Cell Proliferation by Upregulating the Expression of p21 and p27.

Biomed Res Int 2021 13;2021:4708439. Epub 2021 Aug 13.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Tryptophan-2,3-dioxygenase (TDO2) converts tryptophan into kynurenine in the initial limiting step of the kynurenine pathway. During the past decade, the overexpression of TDO2 has been found in various human tumors. However, the role of TDO2 in hepatocellular carcinoma is controversial, and we sought to clarify it in this study.

Methods: Western blot analysis and immunochemistry were used to detect the expression of TDO2 in human tissue specimens. The effect of TDO2 on cell proliferation in vitro was assessed using CCK8 and colony formation assays, and a xenograft mouse model was used to detect the effect of TDO2 on tumor growth in vivo. Flow cytometry was used to assess the cell cycle status.

Results: Low TDO2 expression was found in HCC and was associated with poor prognosis and adverse clinical outcomes. Conversely, TDO2 could restrain the proliferation of HCC cells in vivo and in vitro. Furthermore, TDO2 upregulated the expression of p21 and p27, inducing cell-cycle arrest.

Conclusions: The loss of TDO2 expression in HCC was correlated with a poor prognosis and adverse clinical outcomes. At the same time, TDO2 could restrain the growth of HCC in vivo and in vitro. The results indicate that TDO2 is a potential biomarker and therapeutic target for HCC.
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http://dx.doi.org/10.1155/2021/4708439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378971PMC
August 2021

The CBM48 domain-containing protein FLO6 regulates starch synthesis by interacting with SSIVb and GBSS in rice.

Plant Mol Biol 2021 Aug 13. Epub 2021 Aug 13.

Key Laboratory of Crop Genetics and Physiology of Jiangsu Province, Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding, Yangzhou University, Yangzhou, 225009, China.

Key Message: FLO6 is involved in starch synthesis by interacting with SSIVb and GBSS in rice. Starch synthesized and stored in plastids including chloroplasts and amyloplasts plays a vital role in plant growth and provides the major energy for human diet. However, the molecular mechanisms by which regulate starch synthesis remain largely unknown. In this study, we identified and characterized a rice floury endosperm mutant M39, which exhibited defective starch granule formation in pericarp and endosperm, accompanied by the decreased starch content and amylose content. The abnormal starch accumulation in M39 pollen grains caused a significant decrease in plant fertility. Chloroplasts in M39 leaves contained no or only one large starch granule. Positional cloning combined with complementary experiment demonstrated that the mutant phenotypes were restored by the FLOURY ENDOSPERM6 (FLO6). FLO6 was generally expressed in various tissues, including leaf, anther and developing endosperm. FLO6 is a chloroplast and amyloplast-localized protein that is able to bind to starch by its carbohydrate-binding module 48 (CBM48) domain. Interestingly, we found that FLO6 interacted with starch synthase IVb (SSIVb) and granule-bound starch synthase (GBSSI and GBSSII). Together, our results suggested that FLO6 plays a critical role in starch synthesis through cooperating with several starch synthesis enzymes throughout plant growth and development.
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http://dx.doi.org/10.1007/s11103-021-01178-0DOI Listing
August 2021

Functionalized Silicon Electrodes Toward Electrostatic Catalysis.

Front Chem 2021 27;9:715647. Epub 2021 Jul 27.

Institute of Quantum and Sustainable Technology (IQST), School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, China.

Oriented external electric fields are now emerging as "smart effectors" of chemical changes. The key challenges in experimentally studying electrostatic catalysis are (i) controlling the orientation of fields along the reaction axis and (ii) finely adjusting the magnitudes of electrostatic stimuli. Surface models provide a versatile platform for addressing the direction of electric fields with respect to reactants and balancing the trade-off between the solubility of charged species and the intensity of electric fields. In this mini-review, we present the recent advances that have been investigated of the electrostatic effect on the chemical reaction on the monolayer-functionalized silicon surfaces. We mainly focus on elucidating the mediator/catalysis role of static electric fields induced from either solid/liquid electric double layers at electrode/electrolyte interfaces or space charges in the semiconductors, indicating the electrostatic aspects is of great significance in the semiconductor electrochemistry, redox electroactivity, and chemical bonding. Herein, the functionalization of silicon surfaces allows scientists to explore electrostatic catalysis from nanoscale to mesoscale; most importantly, it provides glimpses of the wide-ranging potentials of oriented electric fields for switching on/off the macroscale synthetic organic electrochemistry and living radical polymerization.
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http://dx.doi.org/10.3389/fchem.2021.715647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353247PMC
July 2021

Summary report of seven cases of COVID-19 infection in renal transplant recipients.

Transpl Immunol 2021 Aug 10;69:101445. Epub 2021 Aug 10.

Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China. Electronic address:

The coronavirus disease 2019 (COVID-19) has swept the world, posing a serious threat to people's lives and health. Several cases of COVID-19 infection in renal transplant recipients (RTRs) have been reported, but the treatment and prognosis have not been fully elucidated. We followed-up with RTRs infected with SARS-CoV2 in our center and classified them as five clinical types-asymptomatic, mild, moderate, severe, and critical. The immunosuppressive agents were not adjusted in asymptomatic carriers and mild patients, the former was mainly treated by isolation, and the latter was treated by low-dose intravenous immunoglobulin (IVIG) to enhance immunity. For moderate or severe patients, the immunosuppressive agents were largely reduced or even interrupted, low-dose IVIG was adopted, and low-dose methylprednisolone (MP) was used to inhibit inflammation and rejection. Immunosuppressants were discontinued early in critical patients; IVIG, high-dose MP, and antibiotics were used. Meanwhile, all patients received at least one antiviral drugs. After aggressive treatment, three patients developed acute kidney injury, and two showed reversal, while the remaining one lost the allograft kidney; one patient died, while other patients were discharged. For different clinical types of RTRs infected with COVID-19, personalized therapies were essential, Meanwhile, patients with COVID-19 infection may have different outcomes due to their different clinical manifestations.
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http://dx.doi.org/10.1016/j.trim.2021.101445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352666PMC
August 2021

AMBRA1 promotes TGF-β signaling via non-proteolytic polyubiquitylation of Smad4.

Cancer Res 2021 Aug 6. Epub 2021 Aug 6.

Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University

Transforming growth factor-β (TGF-β) is pro-metastatic in advanced cancers and its biological activities are mainly mediated by the Smad family of proteins. Smad4 is the central signal transducer and transcription factor in the TGF-β pathway, yet the underlying mechanisms that govern transcriptional activities of Smad4 are not fully understood. Here, we show that AMBRA1, a member of the DDB1 and CUL4-associated factor (DCAF) family of proteins, serves as the substrate receptor for Smad4 in the CUL4-RING (CRL4) ubiquitin ligase complex. The CRL4-AMBRA1 ubiquitin ligase mediates non-proteolytic polyubiquitylation of Smad4 to enhance its transcriptional functions. Consequently, AMBRA1 potentiated TGF-β signaling and critically promoted TGF-β-induced epithelial-to-mesenchymal transition, migration, and invasion of breast cancer cells. Mouse models of breast cancer demonstrated that AMBRA1 promotes metastasis. Collectively, these results show that CRL4-AMBRA1 facilitates TGF-β-driven metastasis by increasing Smad4 polyubiquitylation, suggesting AMBRA1 may serve as a new therapeutic target in metastatic breast cancer.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0431DOI Listing
August 2021

Effects of low frequency multi-mode ultrasound and it's washing solution's interface properties on freshly cut cauliflower.

Food Chem 2022 Jan 23;366:130683. Epub 2021 Jul 23.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China. Electronic address:

This study investigated the effect of single and dual frequency ultrasound washing on freshly cut cauliflower, by pulsed and sweep frequency modes, with or without the addition of zinc acetate (ZA), tea saponin (TS) and ethanol (ET). Results showed that the surface microorganisms were efficiently decreased by sweep dual frequency ultrasound washing. Moreover, the use of 0.5% ZA, or 0.06% TS or 5% ET as washing solution improved the bacterial reduction efficiency. Reducing the interfacial tension, viscosity and contact angle of washing solution may strengthen ultrasound cavitation. Nearly 2.0 log CFU/g natural microorganisms were decreased, and shelf life was extended from 2 to 4-8 days under 4 °C. Physicochemical parameters of bioactive compounds content, enzyme activity, antioxidant ability, freshness were analyzed. Results showed that 0.5% ZA as washing solution of ultrasound washing was beneficial to the quality maintenance during storage period.
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http://dx.doi.org/10.1016/j.foodchem.2021.130683DOI Listing
January 2022

Radically Enhanced Dual Recognition.

Angew Chem Int Ed Engl 2021 Aug 2. Epub 2021 Aug 2.

Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.

Complexation between a viologen radical cation (V ) and cyclobis(paraquat-p-phenylene) diradical dication (CBPQT ) has been investigated and utilized extensively in the construction of mechanically interlocked molecules (MIMs) and artificial molecular machines (AMMs). The selective recognition of a pair of V using radical-pairing interactions, however, remains a formidable challenge. Herein, we report the efficient encapsulation of two methyl viologen radical cations (MV ) in a size-matched bisradical dicationic host - namely, cyclobis(paraquat-2,6-naphthalene) , i.e., CBPQN . Central to this dual recognition process was the choice of 2,6-bismethylenenaphthalene linkers for incorporation into the bisradical dicationic host. They provide the space between the two bipyridinium radical cations in CBPQN suitable for binding two MV with relatively short (3.05-3.25 Å) radical-pairing distances. The size-matched bisradical dicationic host was found to exhibit highly selective and cooperative association with the two MV in MeCN at room temperature. The formation of the tetrakisradical tetracationic inclusion complex - namely, [(MV) ⊂CBPQN] - in MeCN was confirmed by VT H NMR, as well as by EPR spectroscopy. The solid-state superstructure of [(MV) ⊂CBPQN] reveals an uneven distribution of the binding distances (3.05, 3.24, 3.05 Å) between the three different V , suggesting that localization of the radical-pairing interactions has a strong influence on the packing of the two MV inside the bisradical dicationic host. Our findings constitute a rare example of binding two radical guests with high affinity and cooperativity using host-guest radical-pairing interactions. Moreover, they open up possibilities of harnessing the tetrakisradical tetracationic inclusion complex as a new, orthogonal and redox-switchable recognition motif for the construction of MIMs and AMMs.
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http://dx.doi.org/10.1002/anie.202109647DOI Listing
August 2021

Liquid-liquid phase separation in human health and diseases.

Signal Transduct Target Ther 2021 Aug 2;6(1):290. Epub 2021 Aug 2.

Institutes of Biology and Medical Science, Soochow University, Suzhou, People's Republic of China.

Emerging evidence suggests that liquid-liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases. In this review, we describe our current understanding of LLPS and summarize its physiological functions. We further describe the role of LLPS in the development of human diseases. Additionally, we review the recently developed methods for studying LLPS. Although LLPS research is in its infancy-but is fast-growing-it is clear that LLPS plays an essential role in the development of pathophysiological conditions. This highlights the need for an overview of the recent advances in the field to translate our current knowledge regarding LLPS into therapeutic discoveries.
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http://dx.doi.org/10.1038/s41392-021-00678-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326283PMC
August 2021

Interfacial Mo-N-C Bond Endowed Hydrogen Evolution Reaction on [email protected] Carbon Hollow Nanoflowers.

Inorg Chem 2021 Aug 29;60(16):12377-12385. Epub 2021 Jul 29.

College of Science, School of Materials Science and Engineering, China University of Petroleum (East China), Qingdao, Shandong 266580, P. R. China.

Molybdenum diselenide (MoSe) has been considered as promising electrocatalysts for catalyzing the hydrogen evolution reaction (HER) due to its narrow band gap and appropriate adsorption free energy. However, its catalytic performance is still impeded by inferior electrical conductivity and insufficient active sites, thus leading to unsatisfactory HER performance. Herein, [email protected] carbon (NC) hollow nanoflowers with interfacial Mo-N-C bonds were controllably fabricated through the selenization of the self-polymerized Mo-polydopamine precursor. Benefiting from the unique hollow structure, NC protective layer, and intimate interfacial interaction, the optimal [email protected] displays good HER performance with low overpotentials (175 and 183 mV) and long-term stability (up to 12 h at -10 mA cm) in 0.5 M HSO and 1.0 M KOH solutions, respectively. The theoretical results show that Mo-N-C bonds at the interface of [email protected] give rise to relatively low unoccupied e orbital density of states and ideal H adsorption free energy. This work presented here highlights the critical role of interfacial chemical bonds in regulating the electronic structure of nanomaterials and further improving the HER performance.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01600DOI Listing
August 2021

Detection of single peptide with only one amino acid modification via electronic fingerprinting using reengineered durable channel of Phi29 DNA packaging motor.

Biomaterials 2021 09 10;276:121022. Epub 2021 Jul 10.

Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA; Center for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH, 43210, USA; College of Medicine, The Ohio State University, Columbus, OH, 43210, USA; Dorothy M. Davis Heart and Lung Research Institute and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA. Electronic address:

Protein post-translational modification (PTM) is crucial to modulate protein interactions and activity in various biological processes. Emerging evidence has revealed PTM patterns participate in the pathology onset and progression of various diseases. Current PTM identification relies mainly on mass spectrometry-based approaches that limit the assessment to the entire protein population in question. Here we report a label-free method for the detection of the single peptide with only one amino acid modification via electronic fingerprinting using reengineered durable channel of phi29 DNA packaging motor, which bears the deletion of 25-amino acids (AA) at the C-terminus or 17-AA at the internal loop of the channel. The mutant channels were used to detect propionylation modification via single-molecule fingerprinting in either the traditional patch-clamp or the portable MinION™ platform of Oxford Nanopore Technologies. Up to 2000 channels are available in the MinION™ Flow Cells. The current signatures and dwell time of individual channels were identified. Peptides with only one propionylation were differentiated. Excitingly, identification of single or multiple modifications on the MinION™ system was achieved. The successful application of PTM differentiation on the MinION™ system represents a significant advance towards developing a label-free and high-throughput detection platform utilizing nanopores for clinical diagnosis based on PTM.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405592PMC
September 2021

[Research and verification of quality evaluation method of Epimedii Folium based on quantitative analysis of multi-components by single marker].

Zhongguo Zhong Yao Za Zhi 2021 Jun;46(11):2843-2851

the Fifth Medical Center,General Hospital of the People's Liberation Army Beijing 100039,China.

The quality control of Epimedii Folium, composed of diverse constituents, is single at present. In view of this, an eva-luation method of 13 chemical constituents based on quantitative analysis of multi-components by single marker(QAMS) was established to further explore the composition differences of raw products and alcohol extracts in different batches and the influence of alcohol extraction on the composition, so as to provide a reference for improving the quality evaluation and control of Epimedii Folium. The fingerprints of different batches of Epimedii Folium were constructed by ultra-high performance liquid chromatography(UPLC) to evaluate the inter-batch consistency. The changes of the flavonoids in Epimedii Folium during alcohol extraction were analyzed based on determined levels and heat map, and the reasons for the changes were preliminarily discussed. With icariin, the quality control component recorded in the Chinese Pharmacopoeia, as the internal reference, the stability of the relative correction factors of chemical components under different conditions was investigated to obtain the relative correction factors. Then the determination results of QAMS and the external standard method were compared to verify the accuracy of QAMS. The results revealed that all batches of Epimedii Folium met the requirements specified in the Chinese Pharmacopoeia, and the fingerprints of Epimedii Folium from the same place of origin exhibited a high similarity. Raw products and alcohol extracts of Epimedii Folium could be clearly distinguished by prenylated flavonoids, which are potential biomarkers for quality control. Additionally, the glycoside hydrolysis in the alcohol extraction was preliminarily explored. The QAMS method has good accuracy, durability, and repeatability in determining 13 chemical components in Epimedii Folium under different experimental conditions. No significant difference in the results obtained by the two methods was observed. This study can provide a reference for comprehensive, rapid and reasonable quality evaluation of Epimedii Folium.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210225.301DOI Listing
June 2021

Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies.

Front Oncol 2021 1;11:658552. Epub 2021 Jul 1.

Institutes of Biology and Medical Science, Soochow University, Suzhou, China.

Breast cancer is the most common malignant tumor in females worldwide. Chemotherapy is the standard breast cancer treatment; however, chemoresistance is often seen in patients with metastatic breast cancer. Owing to high heterogeneity, the mechanisms of breast cancer chemoresistance and metastasis have not been fully investigated. The possible molecular mechanisms of chemoresistance in breast cancer include efflux transporters, signaling pathways, non-coding RNAs, and cancer stem cells. However, to overcome this hurdle, the use of novel clinical strategies such as drug carriers, immunotherapy, and autophagy regulation, are being investigated. The goal of this review is to summarize the current data about the molecular mechanisms of breast cancer chemoresistance and the novel clinical strategies; thus, providing a useful clinical tool to explore optimal treatment for breast cancer.
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http://dx.doi.org/10.3389/fonc.2021.658552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281885PMC
July 2021

Identification and expression analysis of the β-defensin genes in the goat small intestine.

Gene 2021 Oct 16;801:145846. Epub 2021 Jul 16.

Jiangxi Academy of Agricultural Sciences, Nanchang 330200, Jiangxi, China.

Defensins represent a family of cysteine-rich peptides that have broad-spectrum antimicrobial activities and serve as a typical kind of effector molecule in the immunity. Ruminant species have a large number of β-defensins in the absence of α- and θ-defensins. It is well-known that the genomes of sheep and cattle harbor at least 43 and 57 β-defensin genes, respectively. However, the repertoire of the goat β-defensin gene family has not been fully elucidated. In this study, we identified a total of 50 β-defensins from the goat genome, including 48 functional genes and 2 pseudogenes. Cross-species genomic and evolutionary analyses showed that all of the β-defensins in goat chromosomes 8, 13 and 23 present one-to-one orthologous relationships to their sheep and cattle counterparts, whereas some β-defensin genes in goat chromosome 27 are goat-specific. Moreover, we observed that some duplicated genes in goat chromosome 27 may be derived from gene copy number variation, and the annotation of sheep and cattle β-defensins appears to be incomplete in the genome. Importantly, real-time PCR analysis showed that 17 β-defensins are expressed in the small intestine with abundant cBD1s expression. These findings significant increased our knowledge of ruminant β-defensin and provided useful information for genetic studies, as well as providing a foundation for future research exploring the role of defensins in the immune response.
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http://dx.doi.org/10.1016/j.gene.2021.145846DOI Listing
October 2021

Exploring the barriers of patients with diabetic foot complications in China: a qualitative interview study.

Ann Transl Med 2021 May;9(9):792

Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China.

Background: Patients with diabetic foot complications are associated with high rates of morbidity, disability, and mortality. Through findings of qualitative interviews with patients with this disease, we aimed to explore the barriers they encountered, provide evidence to improve the efficacy of medical services, discuss prevention and treatment strategies for future policymakers, and attract widespread attention from the Chinese society.

Methods: Patients with diabetic foot complications were recruited from three tertiary hospitals in China between July to September 2020. Patients were included who had a clinical diagnosis of diabetic foot complications, were 18 years or older, spoke Chinese as their first language, and were willing to share treatment experiences. An interview guide was used during the in-person semi-structured interviews that lasted 20 to 50 minutes and were audio-recorded. Transcripts were analyzed for qualitative themes.

Results: Forty-one patients (range, 38-79 years; 12 men, 29 women) were recruited. Data analysis indicated five thematic dimensions on barriers encountered by patients with diabetic foot complications: hospital visits, doctor-patient communication, mental burden, economic burden, and social support.

Conclusions: Patients with diabetic foot complications face serious financial, mental, and social burdens in China. Future studies can use the five dimensions to help solve the existing problems and improve treatment outcomes of this patient population.
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http://dx.doi.org/10.21037/atm-20-7569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246227PMC
May 2021
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