Publications by authors named "Chao Zhang"

4,048 Publications

  • Page 1 of 1

Differential Subsampling with Cartesian Ordering Contrast-Enhanced Magnetic Resonance Angiography for the Preoperative Assessment of Anterolateral Thigh Flap.

Korean J Radiol 2022 Jun 20. Epub 2022 Jun 20.

MR Research China, GE Healthcare, Beijing, China.

Objective: To investigate the clinical application of differential subsampling with Cartesian ordering (DISCO) contrast-enhanced (CE) magnetic resonance angiography for anterolateral thigh (ALT) flap transplantation, using operative findings as a reference.

Materials And Methods: Thirty patients (21 males and nine females; mean age ± standard deviation, 45.5 ± 15.6 years) who were scheduled to undergo reconstruction with ALT flaps between June 2020 and June 2021 were included in the prospective study. Before ALT flap transplantation, patients were scanned using CE-DISCO imaging. All acquired DISCO images of the 60 lower limbs (both sides from each patient) were analyzed using maximum intensity projection and volume rendering methods. Two experienced radiologists were employed to examine the patterns of the lateral circumflex femoral artery (LCFA), its branches, and perforators and their skin termini, which were compared with the operative findings.

Results: Using CE-DISCO, the patterns of the LCFA and its branches were clearly identified in all patients. Four different origins of the LCFA were found among the 60 blood vessels: type I (44/60, 73.3%), type II (6/60, 10.0%), type III (8/60, 13.3%), and type IV (2/60, 3.3%). Owing to a lack of perforators entering the skin, two patients did not undergo ALT flap transplantation. For the remaining 28 patients, the ALT flaps in 26 patients were successfully operated without flap re-selection during the operation, while the remaining two patients underwent other surgical procedures due to the thin diameter of the perforator or injury of the perforator during the operation. The success rate of flap transplantation was 92.8% (26/28). All transplanted flaps exhibited good blood supply and achieved primary healing without infection or delayed healing.

Conclusion: CE-DISCO imaging can be an effective method for preoperative perforator imaging before ALT flap transplantation.
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http://dx.doi.org/10.3348/kjr.2021.0696DOI Listing
June 2022

Sensitivity analysis of factors influencing pollutant removal from shallow groundwater by the PRB method based on numerical simulation.

Environ Sci Pollut Res Int 2022 Jun 24. Epub 2022 Jun 24.

School of Resources and Environmental Engineering, Hefei University of Technology, Hefei, 230009, China.

Permeable reactive barrier (PRB) is one of the most promising in situ treatment methods for shallow groundwater pollution. However, optimal design of PRB is very difficult due to a lack of comprehensive understanding of various complex influencing factors of PRB remediation. In this study, eight of the main factors of PRB, including hydraulic gradient I, permeability coefficient K of PRB material, PRB length L, PRB width W, PRB distance from pollution source Dist., the ratio of the maximum adsorption capacity to Langmuir constant of PRB material Q/K, the discharge rate of pollution source DR, and recharge concentration RC were investigated, to carry out the sensitivity analysis of PRB removal efficiency. The simulation experiments for Morris analysis were designed, and pollutant removal efficiency was numerically simulated by coupling MODFLOW and MT3DMS under two scenarios of high and low permeability and dispersivity. For a typical low permeability with low dispersity medium, the sensitivity ranking of factors from high to low is DR, RC, I, W, L, Dist., Q/K, and K, and for a typical high permeability with a high dispersity medium, the sensitivity ranking of factors from high to low is I, W, DR, Q/K, L, RC, Dist., and K. When considering multiple factors in PRB design, the greater the K, L, W, Q/K is, the higher the removal efficiency is; the greater the RC, I is, the lower the removal efficiency is. The rest factors remain ambiguous enhancement to removal efficiency.
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http://dx.doi.org/10.1007/s11356-022-21406-4DOI Listing
June 2022

Aggregation-induced Emission (AIE) and Magnetic Resonance Imaging Characteristics for Targeted and Image-guided siRNA Therapy of Hepatocellular Carcinoma.

Adv Healthc Mater 2022 Jun 24:e2200579. Epub 2022 Jun 24.

Shanghai Institute of Transplantation, Shanghai, 200127, China.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains a global health challenge. Small interfering RNA (siRNA) is a promising therapeutic modality that blocks multiple disease-causing genes without impairing cell structures. However, siRNA therapeutics still have off-target proportion and lack effective quantitative analysis method in vivo. Thus, a novel theragnostic nanoparticle with dual-mode imaging was synthesized for targeted and image-guided siRNA therapy of HCC. Survivin siRNA was carried by Poly ethylenimine (PEI) and interacted with T7-AIE/Gd NPs, which were self-assembled of DSPE-PEG-DTPA(Gd), DSPE-PEG-Mal, DSPE-PEG-PEI, and TPE. The resulting theragnostic nanoparticles exhibited lower toxicity and high therapeutic effect, and excellent T1-weighted MRI and AIE imaging performance. Moreover, in vivo MRI and AIE imaging indicate that this kind of theragnostic nanoparticles rapidly accumulated in the tumor due to active targeting and enhanced permeability and retention (EPR) effects. [email protected] suppresses HCC tumor growth by inducing autophagy and destabilize DNA integrity in tumor cells. The results suggested that T7-AIE-Gd nanoparticles carrying Survivin siRNA with dual-mode imaging characteristics were promising for targeted and image-guided siRNA therapy of hepatocellular carcinoma. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adhm.202200579DOI Listing
June 2022

Bubble energy generator.

Sci Adv 2022 Jun 24;8(25):eabo7698. Epub 2022 Jun 24.

Department of Mechanical Engineering, City University of Hong Kong, Hong Kong 999077, China.

Bubbles have been extensively explored as energy carriers ranging from boiling heat transfer and targeted cancer diagnosis. Yet, despite notable progress, the kinetic energy inherent in small bubbles remains difficult to harvest. Here, we develop a transistor-inspired bubble energy generator for directly and efficiently harvesting energy from small bubbles. The key points lie in designing dielectric surface with high-density electric charges and tailored surface wettability as well as transistor-inspired electrode configuration. The synergy between these features facilitates fast bubble spreading and subsequent departure, transforms the initial liquid/solid interface into gas/solid interface under the gating of bubble, and yields an output at least one order of magnitude higher than existing studies. We also show that the output can be further enhanced through rapid bubble collapse at the air/liquid interface and multiple bubbles synchronization. We envision that our design will pave the way for small bubble-based energy harvesting in liquid media.
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http://dx.doi.org/10.1126/sciadv.abo7698DOI Listing
June 2022

Immunogenicity and Safety of an Inactivated Enterovirus 71 Vaccine Administered Simultaneously with Hepatitis B Virus Vaccine, Group A Meningococcal Polysaccharide Vaccine, Measles-Rubella Combined Vaccine and Japanese Encephalitis Vaccine: A Multi-Center, Randomized, Controlled Clinical Trial in China.

Vaccines (Basel) 2022 Jun 2;10(6). Epub 2022 Jun 2.

Shandong Provincial Center for Disease Control and Prevention, Jinan 250014, China.

Background: The aim of this study was to investigate the immunogenicity and safety of the enterovirus 71 vaccine (EV71 vaccine) administered alone or simultaneously.

Methods: A multi-center, open-label, randomized controlled trial was performed involving 1080 healthy infants aged 6 months or 8 months from Shandong, Shanxi, Shaanxi, and Hunan provinces. These infants were divided into four simultaneous administration groups and EV71 vaccine separate administration group. Blood samples were collected from the infants before the first vaccination and after the completion of the vaccination. This trial was registered in the Clinical Trials Registry (NCT03519568).

Results: A total of 895 were included in the per-protocol analysis. The seroconversion rates of antibodies against EV71 in four simultaneous administration groups (98.44% (189/192), 94.57% (122/129), 99.47% (187/188) and 98.45% (190/193)) were non-inferior to EV71 vaccine separate administration group (97.93% [189/193]) respectively. Fever was the most common adverse event, the pairwise comparison tests showed no difference in the incidence rate of solicited, systemic or local adverse events. Three serious adverse events related to the vaccination were reported.

Conclusions: The evidence of immunogenicity and safety supports that the EV71 vaccine administered simultaneously with vaccines need to be administered during the same period of time recommended in China.
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http://dx.doi.org/10.3390/vaccines10060895DOI Listing
June 2022

Genome-Wide Analysis and Expression Profiling of the Phenylalanine Ammonia-Lyase Gene Family in .

Int J Mol Sci 2022 Jun 20;23(12). Epub 2022 Jun 20.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Agronomy, Northwest A&F University, Yangling 712100, China.

Phenylalanine ammonia-lyase is one of the most widely studied enzymes in the plant kingdom. It is a crucial pathway from primary metabolism to significant secondary phenylpropanoid metabolism in plants, and plays an essential role in plant growth, development, and stress defense. Although PAL has been studied in many actual plants, only one report has been reported on potato, one of the five primary staple foods in the world. In this study, 14 StPAL genes were identified in potato for the first time using a genome-wide bioinformatics analysis, and the expression patterns of these genes were further investigated using qRT-PCR. The results showed that the expressions of StPAL1, StPAL6, StPAL8, StPAL12, and StPAL13 were significantly up-regulated under drought and high temperature stress, indicating that they may be involved in the stress defense of potato against high temperature and drought. The expressions of StPAL1, StPAL2, and StPAL6 were significantly up-regulated after MeJa hormone treatment, indicating that these genes are involved in potato chemical defense mechanisms. These three stresses significantly inhibited the expression of StPAL7, StPAL10, and StPAL11, again proving that PAL is a multifunctional gene family, which may give plants resistance to multiple and different stresses. In the future, people may improve critical agronomic traits of crops by introducing other PAL genes. This study aims to deepen the understanding of the versatility of the PAL gene family and provide a valuable reference for further genetic improvement of the potato.
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http://dx.doi.org/10.3390/ijms23126833DOI Listing
June 2022

Reversion of MRAP2 Protein Sequence Generates a Functional Novel Pharmacological Modulator for MC4R Signaling.

Biology (Basel) 2022 Jun 7;11(6). Epub 2022 Jun 7.

Fundamental Research Center, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology, Tongji University, Shanghai 201619, China.

As a member of the melanocortin receptor family, melanocortin 4 receptor (MC4R) plays a critical role in regulating energy homeostasis and feeding behavior, and has been proven as a promising therapeutic target for treating severe obesity syndrome. Numerous studies have demonstrated that central MC4R signaling is significantly affected by melanocortin receptor accessory protein 2 (MRAP2) in humans, mice and zebrafish. MRAP2 proteins exist as parallel or antiparallel dimers on the plasma membrane, but the structural insight of dual orientations with the pharmacological profiles has not yet been fully studied. Investigation and optimization of the conformational topology of MRAP2 are critical for the development of transmembrane allosteric modulators to treat MC4R-associated disorders. In this study, we synthesized a brand new single transmembrane protein by reversing wild-type mouse and zebrafish MRAP2 sequences and examined their dimerization, interaction and pharmacological activities on mouse and zebrafish MC4R signaling. We showed that the reversed zebrafish MRAPa exhibited an opposite function on modulating zMC4R signaling and the reversed mouse MRAP2 lost the capability for regulating MC4R trafficking but exhibited a novel function for cAMP cascades, despite proper expression and folding. Taken together, our results provided new biochemical insights on the oligomeric states and membrane orientations of MRAP2 proteins, as well as its pharmacological assistance for modulating MC4R signaling.
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http://dx.doi.org/10.3390/biology11060874DOI Listing
June 2022

Variation behavior of organic compounds in melamine-urea-formaldehyde impregnated bond paper in different pyrolysis stages.

J Hazard Mater 2022 08 26;436:129237. Epub 2022 May 26.

Shenzhen Engineering Laboratory for Eco-efficient Recycled Materials, School of Environment and Energy, Peking University Shenzhen Graduate School, China. Electronic address:

Melamine-urea-formaldehyde impregnated bond paper (MUF) is widely used as panel coating and decorative raw paper. Inappropriate treatment of MUF may lead to environmental pollution. In this study, routine MUF and MUF treated with additional titanium (MUF-T) were subjected to fast pyrolysis, and the product properties at different temperatures were investigated. The pyrolysis temperature was selected considering the reaction stages determined by Gaussian curve-fitting on thermogravimetric analysis curves. It was found that the presence of additional titanium changed the decomposition order of the organic components at 220 °C. Urea-formaldehyde in MUF could be decomposed at 220 °C, which had little effect on other components (melamine and cellulose). However, in terms of MUF-T, the decomposition temperature of urea-formaldehyde was postponed to 244 °C, which means that the pyrolysis strategy needs to choose a temperature higher than 244 °C. The volatiles in MUF-T are more easily converted to bio-gas or bio-oil than those in MUF. However, only CH was observed in the bio-gas generated of MUF-T at 220 °C, indicating that titanium did not catalyze the fracture of oxygen-containing functional groups at low temperatures. Titanium condensed at 550 °C, and the utilization of bio-char may face a problem of titanium particle shedding.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129237DOI Listing
August 2022

Influence of clay mineral content on mechanical properties and microfabric of tailings.

Sci Rep 2022 Jun 23;12(1):10700. Epub 2022 Jun 23.

State Key Laboratory of Geomechanics and Geotechnical Engineering, Institute of Rock and Soil Mechanics, Chinese Academy of Sciences, Wuhan, 430071, Hubei, China.

Clay mineral content has an important influence on the mechanical behaviour of tailings, and this mechanical behaviour significantly affects the stability of tailings dams. X-ray fluorescence (XRF) and X-ray diffraction (XRD) tests were carried out on tailings from three different regions. The chemical and mineral composition of the tailings are analyzed. The strength and failure deformation of the tailings were studied by laboratory triaxial compression tests. The effect of clay content on the behaviour of tailings was investigated. The microfabric of tailings sample was examined with the scanning electron microscope (SEM) and nitrogen adsorption tests. The results show that the confining pressure corresponding to the samples exhibiting strain hardening increases with the increase of the content of clay minerals. The cohesion of tailings increases linearly, and the specific surface area decreases as the content of clay minerals increases. Nitrogen adsorption test results reveal from a microscopic point of view that changes in pore structure are associated with the content of clay minerals. The higher the content of clay minerals is, the higher the proportion of micropores is (aggregated interior). Macroscopically, the overall porosity decreases and the size of the pores increases with clay content, which will directly affect the mechanical properties of tailings.
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http://dx.doi.org/10.1038/s41598-022-15063-3DOI Listing
June 2022

Epidemiological Characteristics of Patients Operated for Achilles Tendon Rupture in Shanghai.

Orthop Surg 2022 Jun 22. Epub 2022 Jun 22.

Department of Orthopedic Surgery, Huashan Hospital, Fudan University, Shanghai, China.

Objective: To reflect the potential epidemiological characteristics of Achilles tendon (AT) rupture in Shanghai, China, which has been rarely reported before.

Methods: This work is a descriptive epidemiology study. A total of 302 cases of AT rupture admitted to our department between 01/2013 and 02/2020 are analyzed according to telephone follow-up and medical records. Male to female ratio is 10.3 and the average age is 37.5 years. The record of each case includes age, gender, Body mass index (BMI), quinolone use, corticoid exposure and related medical history/comorbidities. If the case is sports-related (SR), details including kind of sports, intensity of exercise, exercise time before rupture, specific action that causes rupture and situation of warm-up are collected. Two independent sample t-tests and Pearson chi-square tests are used for statistical analysis.

Results: A total of 252 ruptures are SR. Male to female ratio is 15.6 in SR cases. Most SR ruptures occur in patients aged 25-39 years. Ball games are major sports responsible for rupture: basketball in 95 (37.7%), badminton in 68 (27.0%) and soccer in 62 (24.6%). Acceleration and running start is the specific action that cause most (37.7%) ruptures. AT cases are observed in 91 patients with warm-up and 161 without preparation before exercise. As a result, more ruptures happened within 10 min' sports in 161 unprepared (22.4%) than in 91 prepared (5.5%) cases. In SR cases, 107 and 145 cases are observed on weekends and weekdays. Of the 302 total cases, 64 are associated with Achilles tendinopathy. Frequently reported factors such as quinolone use and corticoid exposure are found only in two and 11 of all cases, respectively.

Conclusion: Middle-aged males are common victims of AT rupture in Shanghai. Sports including basketball, badminton, soccer and actions involving in sudden and severe contraction of AT cause most ruptures. Warm-up before exercise reduces rupture in short time. Factors such as quinolone, corticoid and Achilles tendonitis still need attention.
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http://dx.doi.org/10.1111/os.13347DOI Listing
June 2022

Closing Greenhouse Gas Emission Gaps of Staple Crops in China.

Environ Sci Technol 2022 Jun 21. Epub 2022 Jun 21.

College of Resources and Environmental Sciences, National Academy of Agriculture Green Development, Key Laboratory of Plant-Soil Interactions, Ministry of Education, China Agricultural University, Beijing 100193, P. R. China.

China is facing the dual challenge of achieving food security and agricultural carbon neutrality. Developing spatially explicit crop emission profiles can help inform policy to mitigate agricultural greenhouse gases (GHGs), but previous life-cycle studies were conducted mostly at national and provincial levels. Here, we estimate county-level carbon footprint of China's wheat and maize production based on a nationwide survey and determine the contribution of different strategies to closing regional emission gaps. Results show that crop carbon footprint varies widely between regions, from 0.07 to 3.00 kg COe kg for wheat and from 0.09 to 2.30 kg COe kg for maize, with inter-county variation generally much higher than interprovince variation. Hotspots are mainly concentrated in Xinjiang and Gansu provinces, owing to intensive irrigation and high plastic mulch and fertilizer inputs. Closing the regional emission gaps would benefit mostly from increasing crop yields and nitrogen use efficiency, but increasing manure use (e.g., in Northeast, East, and Central China) and energy use efficiency (e.g., in North and Northwest China) can also make important contributions. Our county-level carbon footprint estimates improve upon previous broad-scale results and will be valuable for detailed spatial analysis and the design of localized GHG mitigation strategies in China.
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http://dx.doi.org/10.1021/acs.est.2c01978DOI Listing
June 2022

Sponge-Hosting Polyaniline Array Microstructures for Piezoresistive Sensors with a Wide Detection Range and High Sensitivity.

ACS Appl Mater Interfaces 2022 Jun 21. Epub 2022 Jun 21.

Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, P. R. China.

The development of highly elastic spongy conductors is attractive for use in piezoresistive sensors due to their low cost, easy fabrication, and wide sensing range. However, the combination of high sensitivity and broad sensing range in a single piezoresistive sensor, though highly demanded, is challenging because they are contradictory in principle. Herein, a highly elastic spongy conductor with sponge-hosting polyaniline (PANI) fluff-like array microstructures is fabricated through cryopolymerization. The as-obtained sponge-hosting conductors exhibited an excellent elasticity under high compression strain and stress of up to 80% and 101 kPa, respectively, covering typical deformation ranges for detecting complex human activities. Benefiting from the presence of the sponge-hosting fluff-like PANI arrays, the as-prepared sponge-hosting conductors for piezoresistive sensors possessed a high sensitivity of 0.54 kPa in a broad pressure range of 0.1-101 kPa, ascribing to the formation of the sponge-hosting fluff arrays with graded conductive network structures of array contacts and sponge-skeleton contacts at low and high compressions, respectively. As a result, the as-assembled piezoresistive sensors were demonstrated for tactile sensing and human-motion monitoring. This work reveals new approaches for tailored fabrication of sponge-hosting conducting polymers with tunable fluff-like microstructures for highly sensitive and wide-range wearable piezoresistive sensors.
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http://dx.doi.org/10.1021/acsami.2c07404DOI Listing
June 2022

Habit and goal-related constructs in determining toothbrushing behavior: Two sensor-based longitudinal studies.

Health Psychol 2022 Jul;41(7):463-473

Human-Technology Interaction Group, Department of Industrial Engineering and Innovation Sciences, Eindhoven University of Technology.

Objectives: Two longitudinal studies were conducted to examine how habits and goal-related constructs determine toothbrushing behavior from a dual-process perspective. We aimed to describe the variations of habit strength, intention, and attitude and to test their associations with actual behavior at both inter- and intraindividual levels. In addition, toothbrushing behavior was measured both by self-report and sensors with the goal to compare these measures.

Method: In Study 1, 40 young adults were instructed to brush their teeth twice a day, and their behaviors were measured by accelerometers for 3 weeks. Participants also self-reported their instrumental and affective attitude, habit strength, and behavior frequency weekly. Effects of interest were estimated using structural equation modeling. Study 2 replicated Study 1 with a larger and more diverse sample (N = 79), adding a measure of behavioral intention.

Results: Supporting the dual-process account, habit strength predicted future behavior in addition to goal-related constructs. Habit strength also attenuated the influences of goal-related constructs on behavior, but this pattern only emerged interindividually and for self-reported behavior. In addition, toothbrushing behavior was more strongly driven by affective rather than instrumental attitude. In both studies, associations among variables were weaker within-person and when sensor-measured behavior was modeled.

Conclusions: The partial support for the dual-process account suggests the need of using habit-based interventions to complement intention-based interventions when attempting to change oral health routines. Our findings also highlight the importance of affective aspects of toothbrushing behavior and the potential to incorporate sensor-based objective measures in research and interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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http://dx.doi.org/10.1037/hea0001199DOI Listing
July 2022

Particle-in-Molybdenum Disulfide-Coated Cavity Structure with a Raman Internal Standard for Sensitive Raman Detection of Water Contaminants from Ions to <300 nm Nanoplastics.

J Phys Chem Lett 2022 Jun 21;13(25):5815-5823. Epub 2022 Jun 21.

Shandong Provincial Engineering and Technical Center of Light Manipulation, School of Physics and Electronics, Shandong Normal University, Jinan 250014, P. R. China.

To develop a universal and precise detection strategy that can be applied to water contaminants of various sizes, we designed a particle-in-MoS coated cavity structure of AAO/MoS/Ag with a Raman internal standard. This modified particle-in-cavity structure not only successfully integrates both "surface hot spots" and "volume hot spots" via dressing and manipulating the cascaded optical-field mode inside the cavity but also introduces the chemical enhancement and internal standard attribute of MoS. Because of its unique three-dimensional structure, AAO/MoS/Ag accurately detects water contaminants of various sizes from ions to nanoplastics (<300 nm) for the first time. This work proposes a novel and universal surface-enhanced Raman scattering strategy for detecting multiple-size water contaminants and demonstrates the potential to build a security line in early warning systems for the prevention of water pollution.
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http://dx.doi.org/10.1021/acs.jpclett.2c01534DOI Listing
June 2022

Fully Endoscopic Microvascular Decompression for Hemifacial Spasm Using Improved Retrosigmoid Infrafloccular Approach: Clinical Analysis of 81 Cases.

Oper Neurosurg (Hagerstown) 2022 Jul 20;23(1):40-45. Epub 2022 Apr 20.

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

Background: Microvascular decompression (MVD) is widely accepted as the preferred treatment for hemifacial spasm (HFS). Endoscopy has been implemented to provide a comprehensive view of neurovascular conflicts and minimize the damage caused by brain retraction while exploring the facial nerve root exit zone of the brain stem.

Objective: To preliminarily evaluate the surgical safety and efficacy of fully endoscopic MVD for HFS using an improved retrosigmoid infrafloccular approach.

Methods: The clinical data of 81 patients with HFS who underwent fully endoscopic MVD using an improved endoscopic retrosigmoid infrafloccular approach from June 2019 to December 2020 were retrospectively analyzed. The reliability and advantages of this surgical technique in the treatment of HFS were evaluated according to the intraoperative situation, outcomes of postoperative symptoms, and main complications.

Results: During the follow-up period, 77 cases (95.1%) were completely cured, with immediate facial twitch disappearance in 56 cases and a delayed cure in 21 cases; in 4 cases (4.9%), there was no obvious improvement. There were no cases of recurrence. There were 4 cases (4.9%) of transient facial paralysis after MVD, all of which were completely cured in 3 months. Three cases (3.7%) had hearing loss postoperatively, of whom 2 showed good improvement. At the end of the follow-up period, 1 case (1.2%) still had tinnitus. There were no cases of postoperative intracranial hemorrhage, cerebellar swelling, or death.

Conclusion: Fully endoscopic MVD using an improved retrosigmoid infrafloccular approach not only has the advantages of panoramic surgical visualization but also takes into account the requirements of minimally invasive surgery.
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http://dx.doi.org/10.1227/ons.0000000000000221DOI Listing
July 2022

Energetic bimetallic complexes as catalysts affect the thermal decomposition of ammonium perchlorate.

Dalton Trans 2022 Jun 27;51(25):9894-9904. Epub 2022 Jun 27.

State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081, P. R. China.

Two bimetallic complexes of 4-hydroxy-3,5-dinitropyrazole, [KMn(DNPO)(HO)]·2HO (BMEP-1) and [KZn(DNPO)(HO)] (BMEP-2), were synthesized and characterized by IR spectroscopy and elemental analysis. The crystal structures of BMEP-1 and BMEP-2 were determined by single-crystal X-ray diffraction. It is noteworthy that these complexes presented different metal-organic frameworks. The thermal behaviors of BMEP-1 and BMEP-2 were investigated by differential scanning calorimetry and thermogravimetric analysis measurements. These bimetallic complexes exhibited high thermal stability (348.0 °C and 331.0 °C) due to their large coordination bonds and three-dimensional interconnected structure. The catalytic performances of BMEP-1 and BMEP-2 on the thermal decomposition of ammonium perchlorate were investigated by TGA-DSC, TGA-FTIR, and non-isothermal kinetic analyses. The results showed that BMEP-1 and BMEP-2 exhibited excellent catalytic performance in the thermal decomposition of ammonium perchlorate. Notably, there was only a single exothermic peak at 302.6 °C and 318.6 °C, and the activation energy values of ammonium perchlorate decreased to 123.88 kJ mol and 128.43 kJ mol, respectively. TGA-FTIR results showed that BMEP-1 and BMEP-2, as effective components of catalysis, will promote the production of HO, NO, NO, and HCl in advance, during the thermal decomposition of ammonium perchlorate. BMEP-1 and BMEP-2 are expected to be two candidate additives for the catalytic decomposition of ammonium perchlorate in composite solid propellants.
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http://dx.doi.org/10.1039/d2dt00593jDOI Listing
June 2022

The Oxidative Damage and Inflammation Mechanisms in GERD-Induced Barrett's Esophagus.

Front Cell Dev Biol 2022 26;10:885537. Epub 2022 May 26.

Department of General Surgery, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital of Capital Medical University, Beijing, China.

Barrett's esophagus is a major complication of gastro-esophageal reflux disease and an important precursor lesion for the development of Barrett's metaplasia and esophageal adenocarcinoma. However, the cellular and molecular mechanisms of Barrett's metaplasia remain unclear. Inflammation-associated oxidative DNA damage could contribute to Barrett's esophagus. It has been demonstrated that poly(ADP-ribose) polymerases (PARPs)-associated with ADP-ribosylation plays an important role in DNA damage and inflammatory response. A previous study indicated that there is inflammatory infiltration and oxidative DNA damage in the lower esophagus due to acid/bile reflux, and gastric acid could induce DNA damage in culture esophageal cells. This review will discuss the mechanisms of Barrett's metaplasia and adenocarcinoma underlying oxidative DNA damage in gastro-esophageal reflux disease patients based on recent clinical and basic findings.
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http://dx.doi.org/10.3389/fcell.2022.885537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199966PMC
May 2022

Non-cancer Causes of Death Following Initial Synchronous Bone Metastasis in Cancer Patients.

Front Med (Lausanne) 2022 2;9:899544. Epub 2022 Jun 2.

Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Purpose: To investigate the non-cancer causes of death (COD) in cancer patients with synchronous bone metastasis (BM) that is based on the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: The retrospective cohort study included malignant cancer patients with synchronous BM diagnosed from 2010 to 2018 in the SEER database. The frequencies and proportion of non-cancer COD were calculated and analyzed in different genders, ages, and races subgroups.

Results: A total of 97,997 patients were deceased and included into the current study and 6,782 patients were died of non-cancer causes with a male predominance ( = 4,515, 66.6%). Around half of deaths ( = 3,254, 48.0%) occurred within 6 months after diagnosis while 721 patients were deceased after 3 years. Lung and bronchus cancer, prostate cancer, breast cancer, kidney and renal pelvis cancer, and liver cancer were proved to be the top five cancer types resulting in non-cancer caused death. Cardiovascular and cerebrovascular diseases were the leading non-cancer cause of death ( = 2,618), followed by COPD and associated conditions ( = 553) and septicemia, infectious and parasitic diseases ( = 544). Sub-analyses stratified by gender, age and race were performed and the similar results with slightly difference were observed.

Conclusions: Cardiovascular and cerebrovascular diseases were the main non-cancer cause of death in cancer patients with synchronous BM. Other non-cancer causes included COPD, septicemia, infectious and parasitic diseases, and so on. These findings should be considered by physicians. Physicians can counsel cancer patients with BM regarding survivorship with death causes screening and focus on prevention of non-cancer deaths.
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http://dx.doi.org/10.3389/fmed.2022.899544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201113PMC
June 2022

Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection.

Front Immunol 2022 2;13:890258. Epub 2022 Jun 2.

Department of Laser and Aesthetic Medicine, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

is a major etiological agent of fungal meningoencephalitis. The outcome of cryptococcosis depends on the complex interactions between the pathogenic fungus and host immunity. The understanding of how manipulates the host immune response through its pathogenic factors remains incomplete. In this study, we defined the roles of a previously uncharacterized protein, Csn1201, in cryptococcal fitness and host immunity. Use of both inhalational and intravenous mouse models demonstrated that the deletion significantly blocked the pulmonary infection and extrapulmonary dissemination of . The hypovirulent phenotype of the Δ mutant was attributed to a combination of multiple factors, including preferential dendritic cell accumulation, enhanced Th1 and Th17 immune responses, decreased intracellular survival inside macrophages, and attenuated blood-brain barrier transcytosis rather than exclusively to pathogenic fitness. The Δ mutant exhibited decreased tolerance to various stressors , along with reduced capsule production and enhanced cell wall thickness under host-relevant conditions, indicating that the deletion might promote the exposure of cell wall components and thus induce a protective immune response. Taken together, our results strongly support the importance of cryptococcal Csn1201 in pulmonary immune responses and disseminated infection.
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http://dx.doi.org/10.3389/fimmu.2022.890258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201341PMC
June 2022

CCL5-Secreting Virtual Memory CD8+ T Cells Inversely Associate With Viral Reservoir Size in HIV-1-Infected Individuals on Antiretroviral Therapy.

Front Immunol 2022 26;13:897569. Epub 2022 May 26.

Medical School of Chinese People's Liberation Army (PLA), Beijing, China.

Recent studies highlighted that CD8+ T cells are necessary for restraining reservoir in HIV-1-infected individuals who undergo antiretroviral therapy (ART), whereas the underlying cellular and molecular mechanisms remain largely unknown. Here, we enrolled 60 virologically suppressed HIV-1-infected individuals, to assess the correlations of the effector molecules and phenotypic subsets of CD8+ T cells with HIV-1 DNA and cell-associated unspliced RNA (CA usRNA). We found that the levels of HIV-1 DNA and usRNA correlated positively with the percentage of CCL4+CCL5- CD8+ central memory cells (T) while negatively with CCL4-CCL5+ CD8+ terminally differentiated effector memory cells (T). Moreover, a virtual memory CD8+ T cell (T) subset was enriched in CCL4-CCL5+ T cells and phenotypically distinctive from CCL4+ T subset, supported by single-cell RNA-Seq data. Specifically, T cells showed superior cytotoxicity potentially driven by T-bet and RUNX3, while CCL4+ T subset displayed a suppressive phenotype dominated by JUNB and CREM. In viral inhibition assays, T cells inhibited HIV-1 reactivation more effectively than non-T CD8+ T cells, which was dependent on CCL5 secretion. Our study highlights CCL5-secreting T cells subset as a potential determinant of HIV-1 reservoir size. This might be helpful to design CD8+ T cell-based therapeutic strategies for cure of the disease.
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http://dx.doi.org/10.3389/fimmu.2022.897569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204588PMC
June 2022

Survival Estimation, Prognostic Factors Evaluation, and Prognostic Prediction Nomogram Construction of Breast Cancer Patients with Bone Metastasis in the Department of Bone and Soft Tissue Tumor: A Single Center Experience of 8 Years in Tianjin, China.

Breast J 2022 31;2022:7140884. Epub 2022 Jan 31.

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Purpose: Bone metastasis in breast cancer remains globally concerned. Accurate survival estimation would be beneficial for clinical decision-making, especially for the patients with potential indications of surgery. Based on a retrospective cohort from China, the study aimed to construct a prognostic prediction nomogram for breast cancer patients with bone metastasis.

Methods: Breast cancer patients with bone metastasis diagnosed between 2009 and 2017 in our department were retrospectively selected. The total cohort was divided into construction and validation cohorts (ratio 7 : 3). A nomogram was constructed to predict the probability of survival, and the performance of model was validated.

Results: A total of 343 patients were enrolled with 243 and 100 patients in construction and validation cohorts, respectively. The median overall survival for the total cohort was 63.2 (95% CI: 52.4-74.0) months. Elevated ALP (HR = 1.71, 95% CI: 1.16-2.51; =0.006), no surgery for breast cancer (HR = 2.19, 95% CI: 1.30-3.70; =0.003), synchronous bone metastasis (HR = 1.98, 95% CI: 1.22-3.22; =0.006), and liver metastasis (HR = 1.68, 95% CI: 1.20-2.37; =0.003) were independent prognostic factors for worse survival. The independent predictors and other five factors (including age at diagnosis, ER status, PR status, Her-2 status, and the performance of bisphosphonate) were incorporated to construct the nomogram. The C-index was 0.714 (95% CI: 0.636-0.792) and 0.705 (95% CI: 0.705) in the construction cohort and validation cohort, respectively. All the calibration curves were close to the 45-degree line, which indicated satisfactory calibration.

Conclusion: A retrospective study aiming at prognostic estimation of breast cancer patients with bone metastasis was designed. Four independent prognostic factors were identified and a prognostic nomogram was constructed with satisfactory discrimination and calibration. The model could be used in survival estimation and individualized treatment planning.
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http://dx.doi.org/10.1155/2022/7140884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187277PMC
June 2022

Cavitation assisted endoplasmic reticulum targeted sonodynamic droplets to enhanced anti-PD-L1 immunotherapy in pancreatic cancer.

J Nanobiotechnology 2022 Jun 16;20(1):283. Epub 2022 Jun 16.

Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310000, China.

Background: Sonodynamic therapy (SDT) induces immunogenic cell death (ICD) in tumors and promises to play an assistive role in immunotherapy in pancreatic cancer. However, the short half-life and limited diffusion distance of reactive oxygen species (ROS) impair ICD induction, especially in tumors with relatively poor blood perfusion and dense stroma.

Results: To address this problem, we fabricated cavitation-assisted endoplasmic reticulum (ER) targeted sonodynamic nanodroplets (PMPS NDs, 329 nm). The good sonodynamic effect and precise endoplasmic reticulum target effect was verified. After intravenous injection, the cRGD peptide modified nanodroplets initially aggregated around the tumor vascular endothelial cells. Stimulated by ultrasound, the liquid-to-gas bubbles began to oscillate and cavitate. This acoustic droplet evaporation strategy facilitated transport of the nanoparticle across the vessel, with deep penetration. This loosened the tumor stroma and facilitated accumulation and penetration of loaded sonosensitizer after 6 h. The modified sonosensitizer can selectively accumulate in the ER to generate a large amount of ROS in situ, inducing potent ER stress, amplified ICD and dendritic cell maturation in vitro and in vivo. Furthermore, the elevated antitumor effect of SDT plus anti-PD-L1 immunotherapy was verified using an orthotopic tumor model.

Conclusions: This study reports a cavitation assisted ER targeted sonodynamic therapy that can enhance the effect of anti-PD-L1 immunotherapy effectively in orthotopic and distant pancreatic cancer.
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http://dx.doi.org/10.1186/s12951-022-01459-wDOI Listing
June 2022

Association between maternal breastfeeding and risk of systemic neoplasms of offspring.

Ital J Pediatr 2022 Jun 16;48(1):98. Epub 2022 Jun 16.

Center for Reproductive Medicine, Taihe Hospital, Hubei University of Medicine, No.32, South Renmin Road, Shiyan, 442000, China.

Background: Breastfeeding might prevent childhood cancer by stimulating the immune system.

Methods: The following databases, including PubMed, Embase, and Cochrane Library, were searched from inception to January 10, 2021.

Results: In dose-dependent manner, there was a statistically significant inverse association between any breastfeeding and the incidence of childhood cancer. There was no evidence that breastfeeding was inversely related to childhood cancer of the skeletal, reproductive, or sensory systems. However, breastfeeding was inversely associated with the incidence of hematological malignancies and cancers of the nervous and urinary systems. Among hematological malignancies, the relationship was significant for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), but not for acute non-lymphocytic leukemia (ANLL), Hodgkin's lymphoma (HL), or non-HL.

Conclusions: The evidences demonstrated that breastfeeding have a potential protective role in preventing selective childhood cancer growth, especially for ALL, AML, cancer of nervous and urinary systems. This study recommended that breastfeeding be extended for as long as possible or maintained for at least 6 months to prevent selective childhood cancer growth.
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http://dx.doi.org/10.1186/s13052-022-01292-9DOI Listing
June 2022

A Novel Radiopathological Grading System to Tailor Recurrence Risk for Pathologic Stage IA Lung Adenocarcinoma.

Semin Thorac Cardiovasc Surg 2022 Jun 13. Epub 2022 Jun 13.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Shantou University Medical College, Shantou, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China. Electronic address:

To validate the efficiency of pathological grading system in pathological stage IA lung adenocarcinoma (LUAD), and explore whether integrating preoperative radiological features would enhance the performance of recurrence discrimination. We retrospectively collected 510 patients with resected stage IA LUAD between January 2012 and December 2019 from Guangdong Provincial People's Hospital (GDPH). Pathological grade classification of each case was based on the International Association for the Study of Lung Cancer (IASLC) pathological staging system. Kaplan-Meier curves was used to assess the power of recurrence stratification. Concordance index (C-Index) and receiver operating characteristic curves (ROC) were used for evaluating the clinical utility of different grading systems for recurrence discrimination. Patients of lower IASLC grade showed improved recurrence-free survival (RFS) (p<0.0001) where numerically difference was found between grade II and grade III (p=0.119). By integrating the IASLC grading system and radiological feature, we found the RFS rate decreased as the novel radiopathological (RP) grading system increased (p<0.0001). The difference of RFS curves between any two groups as per the RP grading system was statistically significant (RP grade I vs RP grade II, p = 0.007; RP grade I vs RP grade III, p<0.0001; RP grade II vs RP grade III, p=0.0003). Compared with the IASLC grading system, the RP grading system remarkably improved recurrence survival discrimination (C-index: 0.822; area under the curve, 0.845). Integrating imaging feature into pathological grading system enhanced the efficiency of recurrence discrimination for resected stage IA LUAD and might help conduct subsequent management.
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http://dx.doi.org/10.1053/j.semtcvs.2022.06.003DOI Listing
June 2022

Gaps of Medication Treatment Management Between Guidelines and Real-World for Inpatients With Type 2 Diabetes in China From Pharmacist's Perspective.

Front Endocrinol (Lausanne) 2022 30;13:900114. Epub 2022 May 30.

Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Background: The prevalence of diabetes mellitus remains high in China, and more cardiovascular and cerebrovascular adverse events due to diabetes mellitus are likely to occur in the future.

Objective: To analyze the gap between the current pharmacotherapy management and the guidelines for inpatients with type 2 diabetes mellitus from the perspective of pharmacists so as to provide a reference for optimal pharmacotherapy management methods and models for patients with type 2 diabetes mellitus.

Methods: The study was a cross-sectional observational study. The study was conducted by investigating and analyzing the use of glucose-lowering drugs, adjustment of blood pressure management strategy, lipid management, weight management, and application of antiplatelet drugs in type 2 diabetes inpatients.

Results: A total of 1086 patients with type 2 diabetes were included. Metformin, glycosidase inhibitors, and basal insulin were the most used among type 2 diabetes inpatients. The use of SGLT-2, GLP-1 RAs, DPP-4, and metformin all showed significant increase. SGLT-2 inhibitors (SGLT-2i) showed the fastest increase from 2020 to 2021 (14.5% vs. 39.6%); However, the application rate of SGLT-2i was low among patients with combined ASCVD, renal insufficiency, and diabetic nephropathy (46.4%, 40.9%, and 45.8% respectively). For patients with substandard blood pressure at admission, the average rate of intervention by endocrinologists for adjusting the antihypertensive regimen during hospitalization was 55.6%, and the application rate of ACEI/ARB drugs reached 64.4%. The application rate of statins among patients with type 2 diabetes was still relatively high, at 78.8%. However, the overall intervention rate for patients with suboptimal LDL-c was only 24.1%. The application rate of antiplatelet agents for patients with ASCVD was 77.6%, which was higher than that for patients without ASCVD.

Conclusion: There is still a gap between the practice of medication treatment management of Chinese inpatients with type 2 diabetes and the guidelines, especially in the application of GLP-1RAs and SGLT-2i in patients with concomitant ASCVD, diabetic nephropathy, and renal insufficiency. Meanwhile, physicians and pharmacists should pay more attention on achieving blood pressure and LDL-c standards in type 2 diabetic patients and provide timely interventions.
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http://dx.doi.org/10.3389/fendo.2022.900114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190279PMC
June 2022

eIF6 as a Promising Diagnostic and Prognostic Biomarker for Poorer Survival of Cutaneous Melanoma.

Front Oncol 2022 30;12:848346. Epub 2022 May 30.

Department of Burn and Plastic Surgery, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.

Background: Skin cutaneous melanoma (SKCM) is the deadliest skin cancer and has the most rapidly increasing incidences among all cancer types. Previous research elucidated that melanoma can only be successfully treated with surgical abscission in the early stage. Therefore, reliable and specific biomarkers are crucial to melanoma diagnosis since it often looks like nevi in the clinical manifestations. Moreover, identifying key genes contributing to melanoma progression is also highly regarded as a potential strategy for melanoma therapy. In this respect, translation initiator eIF6 has been proved as a pro-tumor factor in several cancers. However, the role of eIF6 in the skin cutaneous melanoma progression and its potential as a prognostic marker is still unexplored.

Methods: The immunochemical analysis of clinical specimens were served to assess eIF6 expression levels. Gene Expression Profiling Interactive Analysis (GEPIA) database consultations allowed us to find the survival rates of the eIF6-overexpressed patients. eIF6 cellular effects were evaluated in an eIF6-overexpressed A375 cell line constructed with a lentivirus. The analysis of down-stream effectors or pathways was conducted using C-Bioportal and STRING databases.

Results: Our results revealed that eIF6 was highly over-expressed in melanomas compared to normal skin specimens, and thus the abnormally high level of eIF6 can be a diagnostic marker for melanoma. The in silica analysis indicated that patients with eIF6 over-expression had lower survival rates than that low-expression in SKCM. Meanwhile, similar results also could be found in the other four types of cancers. , over-expression of eIF6 increased the proliferation and migration of melanoma cells. Correspondingly, pan-cancer clustering analysis indicated the expression level of intermediate filament proteins was correlated with that of eIF6 expression. In our study, all over-expressed keratin proteins, in accordance with over-expressed eIF6, had a negative correlation with melanoma prognosis. Moreover, the decreased methylation level of keratin genes suggested a new potential regulation mode of eIF6.

Conclusions: The up-regulated eIF6 could be a potential diagnostic and prognostic biomarker of melanoma. This study also provides insights into the potential role of eIF6 in pan-cancer epigenetic regulation.
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http://dx.doi.org/10.3389/fonc.2022.848346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189357PMC
May 2022

Oral pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome: A systematic review and network meta-analysis of randomised controlled trials.

EClinicalMedicine 2022 Jun 20;48:101457. Epub 2022 May 20.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Background: Pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are empirically used. However, the quantitative comparative effectiveness and safety of multiple pharmacological treatments is lacking.

Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to March 22, 2022. Randomised controlled trials comparing two or more oral pharmacological treatments for patients with CP/CPPS were included. Title, abstract, and full-text screening were independently screened by four reviewers. Primary outcomes were efficacy (the National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] total score, pain score, urinary score, and quality of life score [QoL]) and safety (adverse events). This study was registered with PROSPERO, CRD42020184106.

Findings: 25 studies (3514 patients) assessed 26 treatments. Low to very low quality evidence indicated that doxazosin (Mean difference [MD], -11.4, 95% Credible interval [CrI], -17.5 to -5.1) and the doxazosin, ibuprofen, and thiocolchicoside combination (MD, -11.6, CrI, -18.1 to -5.3) were significantly more effective than placebo in the NIH-CPSI total score. Other NIH-CPSI relative outcomes (pain, urinary, and QoL scores) showed a similar pattern. Low and very low quality evidence suggested that combination treatment including doxazosin, ibuprofen, and thiocolchicoside (odds ratios [OR], 3.2, CrI, 0.5 to 19.3) and the tamsulosin and dapoxetine combination (OR, 6.0, CrI, 0.7 to 67.3) caused more adverse events. In half of all comparisons regarding NIH-CPSI pain scores and quality of life scores, heterogeneity was minimal or low. Heterogeneity was high in both NIH-CPSI total symptom scores (  = 78.0%) and pain scores (  = 87. 0%) for tamsulosin versus placebo. There was also high heterogeneity in NIH-CPSI urine scores for the combination of tamsulosin and ciprofloxacin versus tamsulosin (  = 66.8%), tamsulosin and levofloxacin versus tamsulosin (  = 93.3%), and tamsulosin versus placebo (  = 83%).

Interpretation: Pharmacological treatments have little evidence supporting efficacy in CP/CPPS. Future studies could personalise therapy for individuals according to specific symptoms and identify non-pharmacological targets for CP/CPPS.

Funding: Dr Jiani Wu received funding for this project from the China Association for Science and Technology (2017QNRC001), the China Academy of Chinese Medical Sciences (ZZ13-YQ-027), and the National Natural Science Foundation of China (82105037).
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http://dx.doi.org/10.1016/j.eclinm.2022.101457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125656PMC
June 2022

Comprehensive bioinformatics analysis of susceptibility genes for developmental dysplasia of the hip.

Intractable Rare Dis Res 2022 May;11(2):70-80

Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Ji'nan, China.

Developmental dysplasia of the hip (DDH) is a multifactorial disease, which occurs under environmental and genetic influence. The etiopathogenesis of DDH has not been fully explained. As research progresses, many candidate genes have been found to be closely related to the occurrence of DDH. In this study, we comprehensively examined 16 susceptibility genes of DDH using bioinformatics. encodes the pro-alpha1 chains of type I collagen, which is the major protein component of the bone extracellular matrix (ECM). The genes displaying the most statistically significant co-expression link to are , , , , and . DKK1, FRZB and WISP3 are components of the Wnt signaling pathway. CX3CR1 and GDF5 regulate chondrogenesis through the canonical Wnt signaling pathway. ASPN could induce collagen mineralization through binding with collagen and calcium. Integrated bioinformatics analysis indicates that ECM, Wnt signaling pathway and TGF-β signaling pathway are involved in the occurrence of DDH. These provide a basis for further exploring the pathogenesis of DDH.
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http://dx.doi.org/10.5582/irdr.2022.01043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161127PMC
May 2022

SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis.

Proc Natl Acad Sci U S A 2022 Jun 14;119(26):e2122897119. Epub 2022 Jun 14.

Section of Infection and Immunity, Herman Ostrow School of Dentistry, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-κB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes.
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http://dx.doi.org/10.1073/pnas.2122897119DOI Listing
June 2022
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