Publications by authors named "Zhe Hu"

146 Publications

[Effect of moxibustion on the expression of microglia and brain-derived neurotrophic factor protein in the spinal cord of rats with myofascial pain syndrome].

Zhen Ci Yan Jiu 2021 Sep;46(9):769-74

School of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China.

Objective: To observe the effect of moxibustion at myofascial trigger points on microglia activation and the expression of brain-derived neurotrophic factor (BDNF) in the spinal cord of rats with myofascial pain syndrome (MPS), so as to explore the central mechanism of the analgesic effect of moxibustion.

Methods: Twenty-four male SD rats were randomly divi-ded into control, model and moxibustion groups (=8 in each group). The MPS model was established by strinking on fascia musculares and eccentric exercise. Rats in the moxibustion group were treated with mild moxibustion at myofascial trigger point for 15 min, once daily for 7 days. The thermal withdrawal latency (TWL) of rats was measured with a hot stabbing instrument. The pathological changes of the rat medial femoris muscle were observed after H.E. staining. The expressions of microglia marker (OX-42) and BDNF in the spinal dorsal horn were detected by immunohistochemistry and Western blot, separately.

Results: After modeling, the TWL of both the model and the moxibustion groups were significantly down-regulated (<0.01),and were significantly decreased in contrast to that of the control group (<0.01). After treatment and compared with the model group, the TWL of the moxibustion group was significantly increased (<0.01) in the moxibustion group. Rat's muscle fibers of the control group were uniform in thickness and arranged tightly and regularly. While in the model group, some fractures and connective structure tissue renewal, irregular arrangement, and inflammatory cell infiltration were seen. The morphology of muscle fibers in the moxibustion group was close to normal, and the arrangement was neat and orderly, with a small amount of inflammatory cell infiltration. Compared with the control group, the expression of OX-42 and BDNF in the spinal dorsal horn of rats in the model group was increased(<0.01). Following the treatment, and in comparison with the model group, the expression of OX-42 and BDNF of moxibustion group was down-regulated(<0.05).

Conclusion: Moxibustion can significantly improve the injury of the medial femoral muscle and the TWL in MPS rats,which may be related to its effects in inhibiting the activation of spinal dorsal horn microglia and reducing the expression of BDNF.
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http://dx.doi.org/10.13702/j.1000-0607.20210222DOI Listing
September 2021

Health-seeking behavior and barriers to treatment of patients with upper gastrointestinal cancer detected by screening in rural China: real-world evidence from the ESECC trial.

Lancet Reg Health West Pac 2021 Jul 9;12:100181. Epub 2021 Jun 9.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.

Background: To fully realize efficacy in cancer screening, timely and appropriate treatment for participants with malignant lesions is critical. However, the health-seeking behavior of patients with upper gastrointestinal (G.I.) cancer identified in population-level screening programs in China is unknown.

Methods: A community-based real-world investigation was conducted with 136 upper G.I. cancer patients detected in a large screening cohort in an area of high-risk for upper G.I. cancer in China. Using local medical claims data and semi-structured face-to-face interview, we collected information regarding the clinical treatment regimen and factors which result in the lack of timely and appropriate treatment.

Findings: The treatment records for 133 upper G.I. cancer patients were acquired. Among these, 48 (36•09%) patients did not receive treatment within three months of initial diagnosis, and treatment of early-stage cancer was more likely to be delayed. Sixteen patients did not seek further diagnostic testing due to their low health-awareness and socio-economic status. Another 20 participants proactively sought further diagnostic evaluation in health care facilities but were prevented from receiving further treatment due to low sensitivity of given diagnostic test(s), failure to recognize the significance of screening results, and/or lack of basic knowledge of diagnosis and treatment for early cancer on the part of clinicians. The treatment regimen offered to patients depended largely on the level of health care facilities they visited, and non-medical factors were the main reasons for choice of health care facilities.

Interpretation: A coordinated, system-based management strategy is urgently needed to support the design of upper G.I. cancer screening programs in rural populations in China.

Funding: The Charity Project of the National Ministry of Health (201202014), the National Key R & D Program of China (2016YFC0901404), the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), and the National Natural Science Foundation of China (82073626).
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http://dx.doi.org/10.1016/j.lanwpc.2021.100181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356128PMC
July 2021

Dynamic Patterns of N6-Methyladenosine Profiles of Messenger RNA Correlated with the Cardiomyocyte Regenerability during the Early Heart Development in Mice.

Oxid Med Cell Longev 2021 6;2021:5537804. Epub 2021 Aug 6.

Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

N6-Methyladenosine (m6A) plays important roles in regulating mRNA processing. Despite rapid progress in this field, little is known about the role and mechanism of m6A modification in myocardial development and cardiomyocyte regeneration. Existing studies have shown that the heart tissues of newborn mice have the capability of proliferation and regeneration, but its mechanism, particularly its relation to m6A methylation, remains unknown. . To systematically profile the mRNA m6A modification pattern in the heart tissues of mice at different developmental stages, we jointly performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) of heart tissues of mice, respectively, aged 1 day old, 7 days old, and 28 days old. . We identified the linkages and association between differentially expressed mRNA transcripts and hyper or hypomethylated m6A peaks in C57BL/6J mice at different heart developmental stages. Results showed that the amount of m6A peaks and the level of m6A modification were the lowest in the heart of mice at 1 day old. By contrast, heart tissues from 7-day-old mice tended to possess the most m6A peaks and the highest global m6A level. However, the m6A characteristics of myocardial tissue changed little after 7 days old as compared to that of 1 day old. Specifically, we found 1269 downmethylated genes of 1434 methylated genes in 7-day-old mouse heart tissues as compared to those in 1-day-old mice. Hypermethylation of some specific genes may correlate with the heart's strong proliferative and regenerative capability at the first day after birth. In terms of m6A density, the tendency shifted from coding sequences (CDS) to 3'-untranslated regions (3'UTR) and stop codon with the progression of heart development. In addition, some genes demonstrated remarkable changes both in methylation and expression, like kiss1, plekha6, and megf6, which may play important roles in proliferation. Furthermore, signaling pathways highly related to proliferation such as "Wnt signaling pathway," "ECM-receptor interaction," and "cardiac chamber formation" were significantly enriched in 1-day-old methylated genes. . Our results reveal a pattern that different m6A modifications are distributed in C57BL/6J heart tissue at different developmental stages, which provides new insights into a novel function of m6A methylation of mRNA in myocardial development and regeneration.
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http://dx.doi.org/10.1155/2021/5537804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369182PMC
August 2021

CCDC65 as a new potential tumor suppressor induced by metformin inhibits activation of AKT1 via ubiquitination of ENO1 in gastric cancer.

Theranostics 2021 13;11(16):8112-8128. Epub 2021 Jul 13.

Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, 510315 Guangzhou, China.

The coiled-coil domain containing protein members have been well documented for their roles in many diseases including cancers. However, the function of the coiled-coil domain containing 65 (CCDC65) remains unknown in tumorigenesis including gastric cancer. CCDC65 expression and its correlation with clinical features and prognosis of gastric cancer were analyzed in tissue. The biological role and molecular basis of CCDC65 were performed via in vitro and in vivo assays and a various of experimental methods including co-immunoprecipitation (Co-IP), GST-pull down and ubiquitination analysis et al. Finally, whether metformin affects the pathogenesis of gastric cancer by regulating CCDC65 and its-mediated signaling was investigated. : Here, we found that downregulated CCDC65 level was showed as an unfavourable factor in gastric cancer patients. Subsequently, CCDC65 or its domain (a.a. 130-484) was identified as a significant suppressor in GC growth and metastasis in vitro and in vivo. Molecular basis showed that CCDC65 bound to ENO1, an oncogenic factor has been widely reported to promote the tumor pathogenesis, by its domain (a.a. 130-484) and further promoted ubiquitylation and degradation of ENO1 by recruiting E3 ubiquitin ligase FBXW7. The downregulated ENO1 decreased the binding with AKT1 and further inactivated AKT1, which led to the loss of cell proliferation and EMT signal. Finally, we observed that metformin, a new anti-cancer drug, can significantly induce CCDC65 to suppress ENO1-AKT1 complex-mediated cell proliferation and EMT signals and finally suppresses the malignant phenotypes of gastric cancer cells. These results firstly highlight a critical role of CCDC65 in suppressing ENO1-AKT1 pathway to reduce the progression of gastric cancer and reveals a new molecular mechanism for metformin in suppressing gastric cancer. Our present study provides a new insight into the mechanism and therapy for gastric cancer.
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http://dx.doi.org/10.7150/thno.54961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315052PMC
August 2021

Deficient sensory and cognitive processing in children with cochlear implants: An event-related potential study.

Hear Res 2021 Sep 17;408:108295. Epub 2021 Jun 17.

Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China; CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, China. Electronic address:

Compared with children having normal hearing (NH), those with cochlear implants (CIs) perform poorly in spoken language comprehension which involves both low-level acoustic encoding and higher-level cognitive processing. Here, we performed an electroencephalography study to portray this brain dynamics of speech perception in CI children. We presented a Mandarin Chinese monosyllable or four-syllable idiom to CI and NH children, and infrequently varied its lexical tone to form a novel monosyllable or pseudo-idiom in an oddball paradigm. The tone contrast embedded in the monosyllables evoked similar mismatch negativities (MMNs) in CI and NH children at an early stage (~200 ms). However, the amplitude of the MMN evoked by the tone contrast in the idiom context was significantly lower in CI children than in NH children. Furthermore, robust late discriminative negativity (LDN) at a late stage (~500 ms) was found only in NH children, but not in CI children. The MMN and LDN findings indicate deficits of low-level acoustic encoding in a complex context (such as an idiom) and higher-level cognitive processing in CI children, respectively. Both deficient sensory and cognitive processing may contribute to the speech perception difficulties in CI children.
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http://dx.doi.org/10.1016/j.heares.2021.108295DOI Listing
September 2021

Developing better ester- and ether-based electrolytes for potassium-ion batteries.

Chem Sci 2021 Jan 15;12(7):2345-2356. Epub 2021 Jan 15.

Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Renewable Energy Conversion and Storage Center, College of Chemistry, Nankai University Tianjin 300071 China

Potassium-ion batteries (PIBs) have attracted extensive attention for next-generation energy storage systems because of the high abundance of potassium resources and low cost. However, the electrochemical performance of PIBs still cannot satisfy the requirements of practical application. One of the most effective strategies to improve the electrochemical performance of PIBs is electrolyte optimization. In this review, we focus on recent advances in ester- and ether-based electrolytes for high-performance PIBs. First, we discuss the requirements and components of organic electrolytes (potassium salts and solvents) for PIBs. Then, the strategies toward optimizing the electrolytes have been summarized, including potassium salt optimization, solvent optimization, electrolyte concentration optimization, and introducing electrolyte additives. In general, the electrolyte optimization methods can adjust the solvation energy, the lowest unoccupied molecular orbital energy level, and the highest occupied molecular orbital energy level, which are beneficial for achieving fast kinetics, stable and highly K-conductive solid-electrolyte interphase layer, and superior oxidation resistance, respectively. Future studies should focus on exploring the effects of composition on electrolyte characteristics and the corresponding laws. This review provides some significant guidance to develop better electrolytes for high-performance PIBs.
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http://dx.doi.org/10.1039/d0sc06537dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179289PMC
January 2021

Design and Mechanism of a Self-Powered and Disintegration-Reorganization-Regeneration Power Supply with Cold Resistance.

Adv Mater 2021 Jul 17;33(30):e2101239. Epub 2021 Jun 17.

Academy for Engineering and Technology, Institute for Electric Light Sources, School of Information Science and Technology, Fudan University, Shanghai, 200433, China.

Up to now, power supplies designed based on the electrochemical reaction principle have had unavoidable defects, in that a complete redox reaction must be formed inside the power supply to operate normally, which makes it unable to be reconstructed and regenerated. Hence, the design and interpretation of this self-powered and disintegration-reorganization-regeneration power supply are generally considered to be almost insurmountable obstacles to haunt both experimenters and theorists. Herein, a self-powered and disintegration-reorganization-regeneration power supply with relatively stable discharge for 8.3 h is realized by the principle of ion-selective diffusion, which regenerates by radical polymerization. Additionally, the mechanism is investigated systematically by molecular dynamics simulation, and this power supply with a variety of self-powered and disintegration-reorganization-regeneration units can discharge continuously at freezing temperatures and variable temperature (0-25 °C). As a hypothetical model, a self-powered and deformable arch bridge with disintegration and reorganization is fabricated. In the future, this power supply is expected to be applied in prosthetic limbs, bionic skins, implantable power supplies, mobile phones, portable computers, wearable devices, etc. Moreover, with the improvement of the stability and discharge life, it could promote major revolutionary breakthroughs in the fields of intelligent industrial automation, smart buildings, intelligent transportation systems, intelligent power systems, etc.
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http://dx.doi.org/10.1002/adma.202101239DOI Listing
July 2021

Emission tuning of highly efficient quaternary Ag-Cu-Ga-Se/ZnSe quantum dots for white light-emitting diodes.

J Colloid Interface Sci 2021 Nov 23;602:307-315. Epub 2021 May 23.

Institute for Electric Light Sources, School of Information Science and Technology, Fudan University, Shanghai 200433, China; Institute of Future Lighting, Academy for Engineering and Technology, Fudan University, Shanghai 200433, China; Zhongshan - Fudan Joint Innovation Center, Zhongshan 528437, China. Electronic address:

With the blooming development of zero-dimensional nanomaterials, I-III-VI alloying quantum dots (QDs) with outstanding photoelectrical properties have emerged to attract much attention as promising environmentally-friendly substitutions for conventional binary Cd-based QDs. In this work, a facile one-pot method was introduced to synthesize unreported quaternary Ag-Cu-Ga-Se/ZnSe (ACGSe/ZnSe) QDs. A relatively high photoluminescence quantum yield (PL QY) of 71.9% and a tunable emission from 510 to 620 nm were successfully achieved. We explored the roles of alloying compositions in ACGSe/ZnSe QDs, inferring that increased Ag proportion would not only lower the V level which leads to the blue shift of emission, but also slow the ZnSe shelling process owing to the larger lattice distortion. At last, the white light-emitting diodes (WLEDs) were fabricated with ACGSe/ZnSe QDs as the conversion layer, indicating that the as-prepared QDs are a promising candidate for further applications.
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http://dx.doi.org/10.1016/j.jcis.2021.05.110DOI Listing
November 2021

Correction: Gadolinium-doped carbon dots with high-performance in dual-modal molecular imaging.

Anal Methods 2021 Jun;13(24):2732

Institute of Future Lighting, Academy for Engineering and Technology, Fudan University, Shanghai, 200433, China and Institute for Electric Light Sources, Fudan University, Shanghai, 200433, China. and Zhongshan - Fudan Joint Innovation Center, Zhongshan, 528437, China.

Correction for 'Gadolinium-doped carbon dots with high-performance in dual-modal molecular imaging' by Le Wang et al., Anal. Methods, 2021, 13, 2442-2449, DOI: 10.1039/d1ay00270h.
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http://dx.doi.org/10.1039/d1ay90078aDOI Listing
June 2021

Is adjuvant therapy a better option for esophageal squamous cell carcinoma patients treated with esophagectomy? A prognosis prediction model based on multicenter real-world data.

Ann Surg 2021 Jun 2. Epub 2021 Jun 2.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China Anyang Cancer Hospital, Henan Province, People's Republic of China Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Information Technology Service, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China Linkdoc AI Research (LAIR), Beijing, People's Republic of China.

Objective: To construct a prediction model for more precise evaluation of prognosis which will allow personalized treatment recommendations for adjuvant therapy in patients following resection of esophageal squamous cell carcinoma (ESCC).

Background: Marked heterogeneity of patient prognosis and limited evidence regarding survival benefit of various adjuvant therapy regimens pose challenges in the clinical treatment of ESCC.

Methods: Based on comprehensive clinical data obtained from 4,129 consecutive patients with resected ESCC in a high-risk region in China, we identified predictors for overall survival (OS) through a two-phase selection based on Cox proportional hazard regression and minimization of Akaike information criterion. The model was internally validated using bootstrapping and externally validated in 1,815 patients from a non-high-risk region in China.

Results: The final model incorporates nine variables: age, sex, primary site, T stage, N stage, number of lymph nodes harvested, tumor size, adjuvant treatment, and hemoglobin level. A significant interaction was also observed between N stage and adjuvant treatment. N1+ stage patients were likely to benefit from addition of adjuvant therapy as opposed to surgery alone, but adjuvant therapy did not improve OS for N0 stage patients. The C-index of the model was 0.729 in the training cohort, 0.723 after bootstrapping, and 0.695 in the external validation cohort. This model outperformed the seventh edition American Joint Committee on Cancer staging system in prognostic prediction and risk stratification.

Conclusion: The prediction model constructed in this study may facilitate precise prediction of survival and inform decision-making about adjuvant therapy according to N stage.
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http://dx.doi.org/10.1097/SLA.0000000000004958DOI Listing
June 2021

Assessment of the efficacy of tuina on treating cervicogenic headache: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(22):e26224

Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun.

Background: Cervicogenic headache is a secondary headache characterized by unilateral headache, symptoms, and signs of neck involvement. It is often worsened by neck movement, sustained awkward head position, or external pressure over the upper cervical or occipital region on the symptomatic side. In this systematic review, we aimed to evaluate the efficacy and safety of massage therapy for the treatment of cervicogenic headache.

Methods: We searched the China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, China Doctoral Dissertations Full-Text Database, China Master's Theses Full-Text Database, Cochrane Central Register of Controlled Trials, PubMed, and Embase. We will select all eligible studies published on or before April 1, 2021. We will use Review Manager 5.4, provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures.

Results: This meta-analysis further confirmed the benefits of tuina in the treatment of cervicogenic headache.

Conclusion: The purpose of this meta-analysis was to explore the effect of tuina on patients with cervicogenic headache and to provide more options for clinicians and patients to treat cervicogenic headache.

Ethics And Dissemination: This systematic review will evaluate the efficacy and safety of tuina in the treatment of cervicogenic headache. Since all the data included were published, the systematic review did not require ethical approval.

Registration Number: INPLASY202150053.
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http://dx.doi.org/10.1097/MD.0000000000026224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183763PMC
June 2021

High-Voltage Cathode α-FeO Nanoceramics for Rechargeable Sodium-Ion Batteries.

ACS Omega 2021 May 10;6(19):12615-12622. Epub 2021 May 10.

College of Electronic and Optical Engineering & College of Microelectronics, Nanjing University of Posts and Telecommunications, Nanjing 210023, China.

Previously, α-FeO nanocrystals are recognized as anode materials owing to their high capacity and multiple properties. Now, this work provides high-voltage α-FeO nanoceramics cathodes fabricated by the solvothermal and calcination processes for sodium-ion batteries (SIBs). Then, their structure and electrical conductivity were investigated by the first-principles calculations. Also, the SIB with the α-FeO nanoceramics cathode exhibits a high initial charge-specific capacity of 692.5 mA h g from 2.0 to 4.5 V at a current density of 25 mA g. After 800 cycles, the discharge capacity is still 201.8 mA h g, well exceeding the one associated with the present-state high-voltage SIB. Furthermore, the effect of the porous structure of the α-FeO nanoceramics on sodium ion transport and cyclability is investigated. This reveals that α-FeO nanoceramics will be a remarkably promising low-cost and pollution-free high-voltage cathode candidate for high-voltage SIBs.
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http://dx.doi.org/10.1021/acsomega.1c00640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154118PMC
May 2021

Novel Solid-State Sodium-Ion Battery with Wide Band Gap NaTi(PO) Nanocrystal Electrolyte.

ACS Omega 2021 May 22;6(17):11537-11544. Epub 2021 Apr 22.

Department of Microelectronics, Delft University of Technology, Delft 2628 CD, the Netherlands.

NaTi(PO) (NTP), a well-known anode material, could be used as a solid wide-band gap electrolyte. Herein, a novel solid-state sodium-ion battery (SSIB) with the thickness of electrolyte up to the millimeter level is proposed. The results of the difference in charge density investigated by the first-principles calculations imply that using the NTP nanocrystals as electrolytes to transport sodium ions is feasible. Moreover, the SSIB exhibits a high initial discharge capacity of 3250 mAh g at the current density of 50 mA g. As compared with other previously reported SSIBs, our results are better than those reported and suggest that the NTP nanocrystals have potential application in SSIBs as solid electrolytes.
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http://dx.doi.org/10.1021/acsomega.1c00664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154011PMC
May 2021

Soft magnetic skin for super-resolution tactile sensing with force self-decoupling.

Sci Robot 2021 Feb;6(51)

Department of Biomedical Engineering, City University of Hong Kong, Hong Kong SAR, China.

Human skin can sense subtle changes of both normal and shear forces (i.e., self-decoupled) and perceive stimuli with finer resolution than the average spacing between mechanoreceptors (i.e., super-resolved). By contrast, existing tactile sensors for robotic applications are inferior, lacking accurate force decoupling and proper spatial resolution at the same time. Here, we present a soft tactile sensor with self-decoupling and super-resolution abilities by designing a sinusoidally magnetized flexible film (with the thickness ~0.5 millimeters), whose deformation can be detected by a Hall sensor according to the change of magnetic flux densities under external forces. The sensor can accurately measure the normal force and the shear force (demonstrated in one dimension) with a single unit and achieve a 60-fold super-resolved accuracy enhanced by deep learning. By mounting our sensor at the fingertip of a robotic gripper, we show that robots can accomplish challenging tasks such as stably grasping fragile objects under external disturbance and threading a needle via teleoperation. This research provides new insight into tactile sensor design and could be beneficial to various applications in robotics field, such as adaptive grasping, dexterous manipulation, and human-robot interaction.
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http://dx.doi.org/10.1126/scirobotics.abc8801DOI Listing
February 2021

Gadolinium-doped carbon dots with high-performance in dual-modal molecular imaging.

Anal Methods 2021 06 17;13(21):2442-2449. Epub 2021 May 17.

Institute of Future Lighting, Academy for Engineering and Technology, Fudan University, Shanghai, 200433, China.

Carbon dots (CDs), possessing unexpected advantages of photostability, biocompatibility and low toxicity, are regarded as novel nanomaterials in fluorescence (FL) imaging. Doping Gd element in CDs makes them have the ability to be used for magnetic resonance (MR) and FL imaging simultaneously. However, CDs reported before exhibit obvious defects like low photoluminescence (PL) quantum yield (QY) or biotoxicity. In this work, we use gadolinium meglumine, a material with relatively low biotoxicity, along with citric acid and diethylenetriamine to synthesize Gd-doped CDs (Gd-CDs) by a one-step hydrothermal method. The prepared Gd-CDs exhibit excitation-independent emission with a PL QY of 78.05% and a longitudinal relaxivity of 7.37 mM S, which endows the composite with high-performance in MR/FL imaging. Meanwhile, the FL intensity of Gd-CDs remains stable in the presence of multiple amino acids, which indicates that the FL imaging effect should not be impacted significantly in microenvironments in vivo. In addition to the inconspicuous cytotoxicity, Gd-CDs could be used efficiently for dual-modal molecular imaging to detect diseases such as tumors in the early stages.
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http://dx.doi.org/10.1039/d1ay00270hDOI Listing
June 2021

Hierarchical TiCT MXene/Carbon Nanotubes for Low Overpotential and Long-Life Li-CO Batteries.

ACS Nano 2021 May 12;15(5):8407-8417. Epub 2021 May 12.

Jiangsu Key Laboratory of Electrochemical Energy Storage Technologies, College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

Electrochemical carbon dioxide conversion at ambient temperature is an efficient route to synchronously provide a continuous power supply and produce useful chemicals such as carbonates. Rigid catalysts with rational morphological and structural design are used to overcome the sluggish reaction kinetics and contribute to a better cycle life in Li-CO batteries. In this report, a two-dimensional TiCT MXene/carbon heterostructure assembled parallel-aligned tubular architecture was delicately synthesized through a self-sacrificial templating method and delivered an ultralow overpotential of 1.38 V at 0.2 A·g. The heterostructure that inherited the high catalytic performance of TiCT MXene and the outstanding stability of carbon material promoted the adsorption of CO and accelerated the decomposition of lithium carbonate, which was proved by and characterizations and density functional theory calculations. The tubular architecture with large surface area was demonstrated to provide a high durability for long cycle life and ensure good contacts among gas, electrolyte, and electrode.
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http://dx.doi.org/10.1021/acsnano.0c10558DOI Listing
May 2021

Remodels the Immunosuppressive Tumor Microenvironment by Combination of Bacillus Calmette-Guérin and Anti-PD-L1 in an Orthotopic Triple-Negative Breast Cancer Mouse Model.

Onco Targets Ther 2021 30;14:2247-2258. Epub 2021 Mar 30.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Background: Targeting immunosuppressive tumor microenvironment (TME) is one of the important therapeutic strategies for triple-negative breast cancer (TNBC). The application of Bacillus Calmette-Guérin (BCG) in the clinical treatment of bladder cancer has shown that BCG is a strong inducer of immune activation and can remodel the immunosuppressive state of the TME. Meanwhile, previous studies have demonstrated that the 4T1 TNBC mouse model does not respond to anti-PD-L1 treatment alone. Therefore, it is necessary to explore the effect of BCG on TNBC, as well as the potential efficacy of BCG combined with anti-PD-L1.

Materials And Methods: In this study, we studied the effects of BCG treatment on the lymphocytes and transcriptome in the TME of an orthotopic TNBC mouse model, and evaluated the efficacy of combination therapy with BCG and anti-PD-L1 on the tumor.

Results: We found that three-dose BCG treatment could significantly inhibit tumor growth, while the single-dose BCG treatment was able to up-regulate the expression of chemokine-related genes and anti-tumor effect genes, down-regulate the expression of immunosuppressive-related genes, and increase tumor-infiltrating lymphocytes. The combination therapy of BCG and anti-PD-L1 has produced a marked oncolytic effect.

Conclusion: These findings emphasize that BCG treatment can relieve the immunosuppressive state of the TME, and indicate that the combination therapy of BCG and anti-PD-L1may be an efficacious treatment measure for TNBC.
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http://dx.doi.org/10.2147/OTT.S294129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020454PMC
March 2021

Facile Synthesis of Birnessite δ-MnO and Carbon Nanotube Composites as Effective Catalysts for Li-CO Batteries.

ACS Appl Mater Interfaces 2021 Apr 5;13(14):16585-16593. Epub 2021 Apr 5.

Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong Innovation Campus, Squires Way, North Wollongong, New South Wales 2522, Australia.

Li-CO batteries are one type of promising energy storage and conversion devices to capture and utilize the greenhouse gas CO, mitigating global temperature rise and climate change. Catalysts that could effectively decompose the discharge product, LiCO, are essential for high-performance Li-CO batteries. Benefiting from the interconnected porous structure, favorable oxygen vacancy, and the synergistic effects between the carbon nanotube (CNT) and layered birnessite δ-MnO, our Li-CO cathodes with the as-prepared [email protected]δ-MnO catalyst can efficiently afford a large reaction surface area and abundant active sites, provide sufficient electron/Li transport pathways, and facilitate electrolyte infiltration and CO diffusion, demonstrating low overpotential and superior cycling stability, which have been proven by both experimental characterization and theoretical computation. It is expected that this work can provide guidance for the design and synthesis of high-performance electrochemical catalysts for Li-CO batteries.
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http://dx.doi.org/10.1021/acsami.1c03229DOI Listing
April 2021

A Low-Strain Potassium-Rich Prussian Blue Analogue Cathode for High Power Potassium-Ion Batteries.

Angew Chem Int Ed Engl 2021 Jun 5;60(23):13050-13056. Epub 2021 May 5.

Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Renewable Energy Conversion and Storage Center (RECAST), College of Chemistry, Nankai University, Tianjin, 300071, China.

Most of the cathode materials for potassium ion batteries (PIBs) suffer from poor structural stability due to the large ionic radius of K , resulting in poor cycling stability. Here we report a low-strain potassium-rich K Ni[Fe(CN) ] ⋅0.49 H O (KNiHCF) as a cathode material for PIBs. The as-prepared KNiHCF cathode can deliver reversible discharge capacity of 62.8 mAh g at 100 mA g , with a high discharge voltage of 3.82 V. It can also achieve a superior rate performance of 45.8 mAh g at 5000 mA g , with a capacity retention of 88.6 % after 100 cycles. The superior performance of KNiHCF cathode results from low-strain de-/intercalation mechanism, intrinsic semiconductor property and low potassium diffusion energy barrier. The high power density and long-term stability of KNiHCF//graphite full cell confirmed the feasibility of K-rich KNiHCF cathode in PIBs. This work provides guidance to develop Prussian blue analogues as cathode materials for PIBs.
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http://dx.doi.org/10.1002/anie.202103475DOI Listing
June 2021

Streptococcus suis MsmK: Novel Cell Division Protein Interacting with FtsZ and Maintaining Cell Shape.

mSphere 2021 03 17;6(2). Epub 2021 Mar 17.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China

Bacteria of different shapes have adopted distinct mechanisms to faithfully coordinate morphogenesis and segregate their chromosomes prior to cell division. Despite recent focuses and advances, the mechanism of cell division in ovococci remains largely unknown. , a major zoonotic pathogen that causes problems in human health and in the global swine industry, is an elongated and ellipsoid bacterium that undergoes successive parallel splitting perpendicular to its long axis. Studies on cell cycle processes in this bacterium are limited. Here, we report that MsmK (ultiple ugar etabolism protein ), an ATPase that contributes to the transport of multiple carbohydrates, has a novel role as a cell division protein in MsmK can display ATPase and GTPase activities, interact with FtsZ via the N terminus of MsmK, and promote the bundling of FtsZ protofilaments in a GTP-dependent manner Deletion of the C-terminal region or the Walker A or B motif affects the affinity between MsmK and FtsZ and decreases the ability of MsmK to promote FtsZ protofilament bundling. MsmK can form a complex with FtsZ , and its absence is not lethal but results in long chains and short, occasionally anuclear daughter cells. Superresolution microscopy revealed that the lack of MsmK in cells leads to normal septal peptidoglycan walls in mother cells but disturbed cell elongation and peripheral peptidoglycan synthesis. In summary, MsmK is a novel cell division protein that maintains cell shape and is involved in the synthesis of the peripheral cell wall. Bacterial cell division is a highly ordered process regulated in time and space and is a potential target for the development of antimicrobial drugs. Bacteria of distinct shapes depend on different cell division mechanisms, but the mechanisms used by ovococci remain largely unknown. Here, we focused on the zoonotic pathogen and identified a novel cell division protein named MsmK, which acts as an ATPase of the ATP-binding cassette-type carbohydrate transport system. MsmK has GTPase and ATPase activities. protein assays showed that MsmK interacts with FtsZ and promotes FtsZ protofilament bundling that relies on GTP. Superresolution microscopy revealed that MsmK maintains cell shape and is involved in peripheral peptidoglycan synthesis. Knowledge of the multiple functions of MsmK may broaden our understanding of known cell division processes. Further studies in this area will elucidate how bacteria can faithfully and continually multiply in a constantly changing environment.
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http://dx.doi.org/10.1128/mSphere.00119-21DOI Listing
March 2021

Delineating the organization of projection neuron subsets in primary visual cortex with multiple fluorescent rabies virus tracing.

Brain Struct Funct 2021 May 12;226(4):951-961. Epub 2021 Mar 12.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.

The impressive functions of the brain rely on an extensive connectivity matrix between specific neurons, the architecture of which is frequently characterized by one brain nucleus/region connecting to multiple targets, either via collaterals of the same projection neuron or several, differentially specified neurons. Delineating the fine architecture of projection neuron subsets in a specific brain region could greatly facilitate its circuit, computational, and functional resolution. Here, we developed multiple fluorescent rabies viruses (RV) to delineate the fine organization of corticothalamic projection neuron subsets in the primary visual cortex (V1). By simultaneously retrograde labeling multiple distinct subsets of corticothalamic projection neurons in V1 from their target nuclei in thalamus (dLGN, LP, LD), we observed that V1-dLGN corticothalamic projection neurons were densely concentrated in layer VI, except for several sparsely scattered neurons in layer V, while V1-LP and V1-LD corticothalamic projection neurons were localized to both layers V and VI. Meanwhile, we observed a fraction of V1 corticothalamic projection neurons targeting two thalamic nuclei, which was further confirmed by fMOST whole-brain imaging. The multiple fluorescent RV tracing tools can be extensively applied to resolve the architecture of projection neuron subsets in certain brain regions, with a strong potential to delineate the computational and functional organization of these brain regions.
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http://dx.doi.org/10.1007/s00429-021-02250-7DOI Listing
May 2021

Ultra-High Initial Coulombic Efficiency Induced by Interface Engineering Enables Rapid, Stable Sodium Storage.

Angew Chem Int Ed Engl 2021 May 6;60(20):11481-11486. Epub 2021 Apr 6.

National Engineering and Research Center for Advanced Polymer Processing Technology, Zhengzhou University, Zhengzhou, 450001, P. R. China.

High initial coulombic efficiency is highly desired because it implies effective interface construction and few electrolyte consumption, indicating enhanced batteries' life and power output. In this work, a high-capacity sodium storage material with FeS nanoclusters (≈1-2 nm) embedded in N, S-doped carbon matrix (FeS /N,S-C) was synthesized, the surface of which displays defects-repaired characteristic and detectable dot-matrix distributed Fe-N-C/Fe-S-C bonds. After the initial discharging process, the uniform ultra-thin NaF-rich (≈6.0 nm) solid electrolyte interphase was obtained, thereby achieving verifiable ultra-high initial coulombic efficiency (≈92 %). The defects-repaired surface provides perfect platform, and the catalysis of dot-matrix distributed Fe-N-C/Fe-S-C bonds to the rapid decomposing of NaSO CF and diethylene glycol dimethyl ether successfully accelerate the building of two-dimensional ultra-thin solid electrolyte interphase. DFT calculations further confirmed the catalysis mechanism. As a result, the constructed FeS /N,S-C provides high reversible capacity (749.6 mAh g at 0.1 A g ) and outstanding cycle stability (92.7 %, 10 000 cycles, 10.0 A g ). Especially, at -15 °C, it also obtains a reversible capacity of 211.7 mAh g at 10.0 A g . Assembled pouch-type cell performs potential application. The insight in this work provides a bright way to interface design for performance improvement in batteries.
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http://dx.doi.org/10.1002/anie.202102368DOI Listing
May 2021

Correction for Yin et al., "Equine Tetherin Blocks Retrovirus Release and Its Activity Is Antagonized by Equine Infectious Anemia Virus Envelope Protein".

J Virol 2021 Feb 24;95(6). Epub 2021 Feb 24.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agriculture Sciences, Harbin, China

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http://dx.doi.org/10.1128/JVI.02163-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094952PMC
February 2021

Escherichia coli FabG 3-ketoacyl-ACP reductase proteins lacking the assigned catalytic triad residues are active enzymes.

J Biol Chem 2021 Jan-Jun;296:100365. Epub 2021 Feb 3.

Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. Electronic address:

The FabG 3-ketoacyl-acyl carrier protein (ACP) reductase of Escherichia coli has long been thought to be a classical member of the short-chain alcohol dehydrogenase/reductase (SDR) family. FabG catalyzes the essential 3-ketoacyl-ACP reduction step in the FAS II fatty acid synthesis pathway. Site-directed mutagenesis studies of several other SDR enzymes has identified three highly conserved amino acid residues, Ser, Tyr, and Lys, as the catalytic triad. Structural analyses of E. coli FabG suggested the triad S138-Y151-K155 to form a catalytically competent active site. To test this hypothesis, we constructed a series of E. coli FabG mutants and tested their 3-ketoacyl-ACP reductase activities both in vivo and in vitro. Our data show that plasmid-borne FabG mutants, including the double and triple mutants, restored growth of E. coli and Salmonella enterica fabG temperature-sensitive mutant strains under nonpermissive conditions. In vitro assays demonstrated that all of the purified FabG mutant proteins maintained fatty acid synthetic ability, although the activities of the single mutant proteins were 20% to 50% lower than that of wildtype FabG. The S138A, Y151F, and K155A residue substitutions were confirmed by tandem mass spectral sequencing of peptides that spanned all three residues. We conclude that FabG is not a classical short-chain alcohol dehydrogenase/reductase, suggesting that an alternative mode of 3-ketoacyl-ACP reduction awaits discovery.
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http://dx.doi.org/10.1016/j.jbc.2021.100365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973133PMC
August 2021

Oral microbiome and risk of malignant esophageal lesions in a high-risk area of China: A nested case-control study.

Chin J Cancer Res 2020 Dec;32(6):742-754

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing 100142, China.

Objective: We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.

Methods: We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China. The oral microbiome was evaluated with 16S ribosomal RNA (rRNA) gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above (SDA) and 168 matched healthy controls. DESeq analysis was performed to identify taxa of differential abundance. Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.

Results: A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls (all P<0.05 & false discovery rate-adjusted Q<0.10). A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve (AUC) of 0.89 (95% CI, 0.84-0.93). Cross-validation and sensitivity analysis, excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls, or restriction to screen-endoscopic-detected or clinically diagnosed case-control triads, or using only bacterial data measured at the baseline, yielded AUCs>0.84.

Conclusions: The oral microbiome may play an etiological and predictive role in esophageal cancer, and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2020.06.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797237PMC
December 2020

Microcatheter-Assisted Circumferential Trabeculotomy versus Conventional Trabeculotomy for the Treatment of Childhood Glaucoma: A Meta-analysis.

Biomed Res Int 2020 4;2020:3716859. Epub 2020 Nov 4.

Affiliated Eye Hospital of Nanchang University, Nanchang Jiangxi, China.

Background: The aim of the current meta-analysis was to compare the efficacy of microcatheter-assisted circumferential trabeculotomy (Group 1) with that of conventional trabeculotomy (Group 2) for the treatment of childhood glaucoma.

Methods: Published studies were systematically searched via the Web of Science, PubMed, Embase, and Cochrane Library databases. Odds ratios and 95% confidence intervals were calculated for dichotomous variables. Mean ± the standard deviation, mean difference, and 95% confidence intervals were calculated for continuous variables. Heterogeneity was assessed. Random effects modeling and RevMan version 5.30 were used to analyze the data.

Results: Five eligible studies were included in the meta-analysis. Mean postoperative intraocular pressures were significantly lower in Group 1 than in Group 2 at 3 months ( = 0.03), 6 months ( = 0.03), and 12 months ( = 0.007) postoperatively. The complete success rates were higher in Group 1 than in Group 2 at 3 months ( = 0.008), 6 months ( = 0.01), and 12 months ( = 0.004) postoperatively, as were the respective qualified success rates ( = 0.04, = 0.0007, and = 0.001). The pooled estimate indicated lower antiglaucoma medication use in Group 1, especially at 1 month postoperatively ( = 0.003).

Conclusions: Microcatheter-assisted circumferential trabeculotomy resulted in excellent intraocular pressure control, higher success rates, and the utilization of less medication than conventional trabeculotomy for childhood glaucoma. Therefore, microcatheter-assisted circumferential trabeculotomy may be recommended as the initial procedure for the treatment of childhood glaucoma.
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http://dx.doi.org/10.1155/2020/3716859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657706PMC
March 2021

BMPQ-1 binds selectively to (3+1) hybrid topologies in human telomeric G-quadruplex multimers.

Nucleic Acids Res 2020 11;48(20):11259-11269

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

A single G-quadruplex forming sequence from the human telomere can adopt six distinct topologies that are inter-convertible under physiological conditions. This presents challenges to design ligands that show selectivity and specificity towards a particular conformation. Additional complexity is introduced in differentiating multimeric G-quadruplexes over monomeric species, which would be able to form in the single-stranded 3' ends of telomeres. A few ligands have been reported that bind to dimeric quadruplexes, but their preclinical pharmacological evaluation is limited. Using multidisciplinary approaches, we identified a novel quinoline core ligand, BMPQ-1, which bound to human telomeric G-quadruplex multimers over monomeric G-quadruplexes with high selectivity, and induced the formation of G-quadruplex DNA along with the related DNA damage response at the telomere. BMPQ-1 reduced tumor cell proliferation with an IC50 of ∼1.0 μM and decreased tumor growth rate in mouse by half. Biophysical analysis using smFRET identified a mixture of multiple conformations coexisting for dimeric G-quadruplexes in solution. Here, we showed that the titration of BMPQ-1 shifted the conformational ensemble of multimeric G-quadruplexes towards (3+1) hybrid-2 topology, which became more pronounced as further G-quadruplex units are added.
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http://dx.doi.org/10.1093/nar/gkaa870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672424PMC
November 2020

The predictive value of serum amyloid A and C-reactive protein levels for the severity of coronavirus disease 2019.

Am J Transl Res 2020 15;12(8):4569-4575. Epub 2020 Aug 15.

Department of Neurology, The First Affiliated Hospital of University of Science and Technology of China Hefei 230001, Anhui Province, China.

This study was designed to assess the levels of human serum amyloid A (SAA) and C-reactive protein (CRP) in patients with coronavirus disease 2019 (COVID-19) to determine their prognostic value in predicting the severity of disease. Patients with COVID-19 who presented with acute respiratory distress syndrome (ARDS) shared distinct characteristics. For example, the patients were older, and had higher levels of inflammatory indicators [i.e., levels of CRP, SAA, procalcitonin (PCT), and interleukin-6; CRP-to-PCT ratio; SAA-to-CRP ratio; and neutrophil-to-lymphocyte ratio (NLR)], higher inflammatory cell counts (i.e., white blood cell count and neutrophil count), and lower lymphocyte counts compared with patients without ARDS. Patients without ARDS still exhibited mild illness and had elevated SAA levels but not CRP levels. In patients with elevated SAA and CRP levels, the NLR was statistically associated with disease severity. According to the receiver operating characteristic curve analysis, the combined predictive probability of CRP and SAA levels, along with white blood cell count, showed the highest area under the curve (AUC; 0.878), and was able to distinguish between patients with and without ARDS. The cut-off level for SAA to predict the severity of COVID-19 was 92.900, with a sensitivity of 95.8%, a specificity of 53.7%, and an AUC of 0.712. For patients with elevated levels of SAA but not CRP, a mild condition was predicted. For patients with elevated levels of both SAA and CRP, and a high NLR, a severe infection was predicted, requiring medical attention. Therefore, CRP and SAA levels demonstrate a prognostic value for predicting the severity of COVID-19.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476119PMC
August 2020

Inverted Internal Limiting Membrane Flap Technique versus Internal Limiting Membrane Peeling for Vitrectomy in Highly Myopic Eyes with Macular Hole-Induced Retinal Detachment: An Updated Meta-Analysis.

J Ophthalmol 2020 24;2020:2374650. Epub 2020 Aug 24.

Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi, China.

Background: The aim of this meta-analysis was to compare morphological and functional outcomes between vitrectomy with the inverted internal limiting membrane (ILM) flap technique and vitrectomy with internal limiting membrane peeling in highly myopic eyes with macular hole- (MH-) induced retinal detachment (MHRD).

Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were comprehensively searched from inception to November 10, 2019, for published studies comparing the two techniques for the treatment of MHRD. The outcomes in the collected articles included the postoperative MH closure rate, retinal reattachment rate, and best-corrected visual acuity (BCVA). Review Manager (version 5.3) was used for analyses.

Results: In total, seven retrospective studies comparing the inverted ILM flap technique with ILM peeling for the treatment of MHRD were included. The MH closure rate was significantly higher in the inverted ILM flap group than in the ILM peeling group at 6 and 12 months after initial surgery (OR = 15.39; 95% CI: 6.68 to 35.43; < 0.00001 and OR = 12.58, 95% CI: 3.51 to 45.08; =0.0001), while the retinal reattachment rate was similar in both groups at 6 months after initial surgery (OR = 2.40; 95% CI: 0.89 to 6.50; =0.08). Besides, the postoperative BCVA was significantly better in the inverted ILM flap group than in the ILM peeling group at 12 months after initial surgery (MD = -0.35; 95% CI: -0.52 to -0.18; < 0.0001).

Conclusions: Thus, the MH closure rate and postoperative BCVA may be better with the inverted ILM flap technique than with ILM peeling for myopic MHRD, while the postoperative retinal reattachment rate appears to be similar with both techniques. Therefore, in the future, vitrectomy with the inverted ILM flap technique should be preferred over standard ILM peeling technique for the treatment of MHRD in highly myopic eyes.
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http://dx.doi.org/10.1155/2020/2374650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463360PMC
August 2020

The primary step of biotin synthesis in mycobacteria.

Proc Natl Acad Sci U S A 2020 09 8;117(38):23794-23801. Epub 2020 Sep 8.

Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

Biotin plays an essential role in growth of mycobacteria. Synthesis of the cofactor is essential for to establish and maintain chronic infections in a murine model of tuberculosis. Although the late steps of mycobacterial biotin synthesis, assembly of the heterocyclic rings, are thought to follow the canonical pathway, the mechanism of synthesis of the pimelic acid moiety that contributes most of the biotin carbon atoms is unknown. We report that the gene annotated as encoding Tam, an -methyltransferase that monomethylates and detoxifies -aconitate, instead encodes a protein having the activity of BioC, an -methyltransferase that methylates the free carboxyl of malonyl-ACP. The Tam functionally replaced BioC both in vivo and in vitro. Moreover, deletion of the gene resulted in biotin auxotrophy, and addition of biotin to cultures repressed gene transcription. Although its pathogenicity precluded in vivo studies, the Tam also replaced BioC both in vivo and in vitro and complemented biotin-independent growth of the deletion mutant strain. Based on these data, we propose that the highly conserved mycobacteria genes be renamed BioC presents a target for antituberculosis drugs which thus far have been directed at late reactions in the pathway with some success.
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http://dx.doi.org/10.1073/pnas.2010189117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519262PMC
September 2020
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