Publications by authors named "Fan Yang"

5,535 Publications

  • Page 1 of 1

Surgical and oncological outcomes of distal gastrectomy compared to total gastrectomy for middle-third gastric cancer: A systematic review and meta-analysis.

Oncol Lett 2022 Sep 4;24(3):291. Epub 2022 Jul 4.

Department of General Surgery, Center for Minimally Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.

Distal gastrectomy (DG) and total gastrectomy (TG) are the most common types of radical surgery for patients with middle-third gastric cancer (MTGC). However, the indications and benefits of the two procedures still remain controversial. The present meta-analysis aimed to compare the surgical and oncological outcomes of DG and TG in the treatment of MTGC. A rigorous literature review was performed in the databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Chinese BioMedical Literature to retrieve studies published up to February 2022. The Newcastle-Ottawa Scale was used to assess the quality of included studies and a meta-analysis was performed using RevMan 5.3 software. A total of 12 retrospective studies performing comparisons of DG and TG were included in the present meta-analysis. For patients who underwent DG, a lower rate of overall post-operative complications, anastomosis leakage and intro-abdominal infection was determined. No significant difference was observed between DG and TG in the 5-year overall survival when the proximal resection margin ranged from 3 to 5 cm. Although DG was associated with a higher 5-year overall survival rate when compared to TG, there was no significant difference in the stratified analyses by TNM stage. In conclusion, the prognosis of MTGC did not depend on the extent of gastrectomy. With lower complications and acceptable oncological outcomes, DG was a safe and feasible surgical procedure for MTGC when a negative proximal margin was confirmed.
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http://dx.doi.org/10.3892/ol.2022.13411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353235PMC
September 2022

Assessment of patient based real-time quality control on comparative assays for common clinical analytes.

J Clin Lab Anal 2022 Aug 10:e24651. Epub 2022 Aug 10.

Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: It is critical for laboratories to conduct multianalyzer comparisons as a part of daily routine work to strengthen the quality management of test systems. Here, we explored the application of patient-based real-time quality controls (PBRTQCs) on comparative assays to monitor the consistency among clinical laboratories.

Methods: The present study included 11 commonly tested analytes that were detected using three analyzers. PBRTQC procedures were set up with exponentially weighted moving average (EWMA) algorithms and evaluated using the AI-MA artificial intelligence platform. Comparative assays were carried out on serum samples, and patient data were collected. Patients were divided into total patient (TP), inpatient (IP), and outpatient (OP) groups.

Results: Optimal PBRTQC protocols were evaluated and selected with appropriate truncation limits and smoothing factors. Generally, similar comparative assay performance was achieved using both the EWMA and median methods. Good consistency between the results from patients' data and serum samples was obtained, and unacceptable bias was detected for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) when using analyzer C. Categorizing patients' data and applying specific groups for comparative assays could significantly improve the performance of PBRTQCs. When monitoring the inter- and intraanalyzer stability on a daily basis, EWMA was superior in detecting very small quality-related changes with lower false-positive alarms.

Conclusions: We found that PBRTQCs have the potential to efficiently assess multianalyzer comparability. Laboratories should be aware of population variations concerning both analytes and analyzers to build more suitable PBRTQC protocols.
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http://dx.doi.org/10.1002/jcla.24651DOI Listing
August 2022

BTLACD200 B cells dictate the divergent immune landscape and immunotherapeutic resistance in metastatic vs. primary pancreatic cancer.

Oncogene 2022 Aug 10. Epub 2022 Aug 10.

S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.

Response to cancer immunotherapy in primary versus metastatic disease has not been well-studied. We found primary pancreatic ductal adenocarcinoma (PDA) is responsive to diverse immunotherapies whereas liver metastases are resistant. We discovered divergent immune landscapes in each compartment. Compared to primary tumor, liver metastases in both mice and humans are infiltrated by highly anergic T cells and MHCIIIL10 macrophages that are unable to present tumor-antigen. Moreover, a distinctive population of CD24CD44CD40 B cells dominate liver metastases. These B cells are recruited to the metastatic milieu by Muc1IL18 tumor cells, which are enriched >10-fold in liver metastases. Recruited B cells drive macrophage-mediated adaptive immune-tolerance via CD200 and BTLA. Depleting B cells or targeting CD200/BTLA enhanced macrophage and T-cell immunogenicity and enabled immunotherapeutic efficacy of liver metastases. Our data detail the mechanistic underpinnings for compartment-specific immunotherapy-responsiveness and suggest that primary PDA models are poor surrogates for evaluating immunity in advanced disease.
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http://dx.doi.org/10.1038/s41388-022-02425-4DOI Listing
August 2022

Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome: a real-world study.

Chin Med J (Engl) 2022 Aug 10. Epub 2022 Aug 10.

Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

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http://dx.doi.org/10.1097/CM9.0000000000002261DOI Listing
August 2022

Development, hotspots and trend directions of groundwater salinization research in both coastal and inland areas: a bibliometric and visualization analysis from 1970 to 2021.

Environ Sci Pollut Res Int 2022 Aug 9. Epub 2022 Aug 9.

Institute of Marine Science and Technology, Shandong University, Binhai Road No. 72, Qingdao, 266237, Shandong Province, China.

As a global concern, the issue of groundwater salinization refers to the phenomenon of an increase in the overall chemical content over background levels in the groundwater. It involves a long-term process that could degrade groundwater quality and restrict its availability for drinking, irrigation and industry. For the effective protection and further research of groundwater resources, policy strongly depends on understanding the development, hotspots and trend directions of groundwater salinization research, which involves the degree, sources and processes of global groundwater salinization. However, such a comprehensive and systematic analysis has not been performed, and it is difficult to have a deeper understanding of groundwater salinization. The purpose of this paper is to analyze the knowledge structure, hot topics and trends in the field of groundwater salinization based on 6651 Web of Science (WoS) publications combined with CiteSpace for in-depth bibliometric and visual analysis. The results showed that 292 institutions in 125 countries have published articles in this field from 1970 to 2021. The USA was one of the most prolific contributors, with the largest number of publications and active institutions. Cooperation among authors has become frequent in recent years, and they tend to cooperate in groups. According to the analysis of co-occurrence keywords and co-cited articles, "water resources", "sea level rise" and "variable density flow" were identified as three hot topics. A keyword burst analysis revealed the emerging trends of concerns about global climate change and the sustainable utilization of water resources. In addition, the possible opportunities and challenges were explored that may be faced in groundwater salinization research. The outcomes of this study are significant for future research on groundwater management and pollution control.
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http://dx.doi.org/10.1007/s11356-022-22134-5DOI Listing
August 2022

Elucidation of the interaction between fructose and key aroma compounds in watermelon juice via Raman spectroscopy and nuclear magnetic resonance.

Food Res Int 2022 Sep 2;159:111613. Epub 2022 Jul 2.

Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University (BTBU), Beijing 100048, China. Electronic address:

Food matrix composition is an important factor affecting the release of aroma compounds. In the present study, four key aroma compounds (namely, hexanal, nonanal, (E)-2-nonenal, and acetophenone) were quantified in watermelon juice by stable isotope dilution assay. Using Raman spectroscopy and H NMR, it was found that hexanal, nonanal, and (E)-2-nonenal combine with fructose via hydrogen bonds, whereas acetophenone interact with fructose via π-π interaction. Entropy compensation at higher temperatures may explain the decrease in the contents of hexanal, nonanal, and (E)-2-nonenal released from the system. In contrast, the decrease in the contents of these aroma compounds by HO might be due to the formation of a greater number of hydrogen bonds with carboxyl groups oxidized by aldehydes. This study contributes to further the understanding on the interaction between aroma compounds and fructose, thus offering practical insights on the regulation and control of flavor development in watermelon juice.
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http://dx.doi.org/10.1016/j.foodres.2022.111613DOI Listing
September 2022

Artificial humic acid facilitates biological carbon sequestration under freezing-thawing conditions.

Sci Total Environ 2022 Aug 5;849:157841. Epub 2022 Aug 5.

Joint Laboratory of Northeast Agricultural University and Max Planck Institute of Colloids and Interfaces (NEAU-MPICI), Harbin 150030, China; School of Water Conservancy and Civil Engineering, Northeast Agricultural University, Harbin 150030, China. Electronic address:

Freezing-thawing events contribute to the accumulation of soil organic matter and the formation of high fertility black soil. On this base, we explore the influence of the combination of liquid artificial humic acid (LA-HA) and freezing-thawing events on strengthening carbon sequestration in soils. The measurements of the total organic carbon (TOC) and dissolved organic carbon (DOC) content illustrate that the applications of LA-HA indeed largely enhanced the persistent carbon reservoirs during freezing-thawing cycles, and the highest TOC net increment was found as up to 4000 mg/kg (0.36 wt% C with the control treatment versus 0.79 wt% C with 300 mL/kg LA-HA (3LA-HA) treatment after 10 freezing-thawing cycles). Spectral analysis reveals that LA-HA treatments accelerated the formation of additional humic substances under freezing-thawing events, i.e., the transformation of labile carbon to resistant carbon. Finally, the results of highthroughput sequencing corresponding to cbbL gene demonstrate that 3LA-HA functioned to optimizing the community structure of carbon sequestration bacteria and improving the dominant position of part bacteria with strong carbon fixation ability to reduce soil carbon loss after thawing, e.g., Mycolicibacterium gadium and Starkeya novella.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157841DOI Listing
August 2022

Rapid determination of 103 common veterinary drug residues in milk and dairy products by ultra performance liquid chromatography tandem mass spectrometry.

Front Nutr 2022 22;9:879518. Epub 2022 Jul 22.

Hebei Food Inspection and Research Institute, Shijiazhuang, China.

A multi-residue method has been developed for the identification and quantification of 103 common veterinary drug residues in milk and dairy Products. This method was based on QuEChERS with dispersive solid-phase where C18 sorbent and anhydrous sodium sulfate were used to sample purification. After evaporation and reconstitution, the samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The mean recovery results were all higher than 60% except ampicillin, pipemidic acid, enoxacin, and estriol, and the relative standard deviation was <20.0%. The limit of quantification ranged between 0.1 and 5 μg/kg for milk and between 0.5 and 25 μg/kg for milk powder. It was successfully used to detect residues of veterinary drug in real samples. This study proposes a simple and fast analytical method for monitoring multi-class veterinary drug residues to ensure food safety.
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http://dx.doi.org/10.3389/fnut.2022.879518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354588PMC
July 2022

Sarcopenic obesity and therapeutic outcomes in gastrointestinal surgical oncology: A meta-analysis.

Front Nutr 2022 22;9:921817. Epub 2022 Jul 22.

Department of Thoracic Surgery, Thoracic Oncology Institute, Peking University People's Hospital, Beijing, China.

Background: Sarcopenic obesity (SO) has been indicated as a scientific and clinical priority in oncology. This meta-analysis aimed to investigate the impacts of preoperative SO on therapeutic outcomes in gastrointestinal surgical oncology.

Methods: We searched the PubMed, EMBASE, and Cochrane Library databases through March 4th 2022 to identify cohort studies. Endpoints included postoperative complications and survival outcomes. Newcastle Ottawa Scale was used for quality assessment. Heterogeneity and publication bias were assessed. Subgroup analyses and sensitivity analyses were performed.

Results: Twenty-six studies (8,729 participants) with moderate to good quality were included. The pooled average age was 65.6 [95% confidence interval (CI) 63.7-67.6] years. The significant heterogeneity in SO definition and diagnosis among studies was observed. Patients with SO showed increased incidences of total complications (odds ratio 1.30, 95% CI: 1.03-1.64, = 0.030) and major complications (Clavien-Dindo grade ≥ IIIa, odds ratio 2.15, 95% CI: 1.39-3.32, = 0.001). SO was particularly associated with the incidence of cardiac complications, leak complications, and organ/space infection. SO was also predictive of poor overall survival (hazard ratio 1.73, 95% CI: 1.46-2.06, < 0.001) and disease-free survival (hazard ratio 1.41, 95% CI: 1.20-1.66, < 0.001). SO defined as sarcopenia in combination with obesity showed greater association with adverse outcomes than that defined as an increased ratio of fat mass to muscle mass. A low prevalence rate of SO (< 10%) was associated with increased significance for adverse outcomes compared to the high prevalence rate of SO (> 20%).

Conclusion: The SO was associated with increased complications and poor survival in gastrointestinal surgical oncology. Interventions aiming at SO have potentials to promote surgery benefits for patients with gastrointestinal cancers. The heterogeneity in SO definition and diagnosis among studies should be considered when interpreting these findings.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255286], identifier [CRD42021255286].
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http://dx.doi.org/10.3389/fnut.2022.921817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355157PMC
July 2022

Effects of alfalfa saponins on the production performance, serum biochemical factors, and immune factors in Small-Tailed Han sheep.

Front Vet Sci 2022 22;9:924373. Epub 2022 Jul 22.

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.

This study aimed to determine the potential effects of alfalfa saponins on the production performance, serum biochemical factors, and immune factors in sheep. Twenty Small-Tailed Han sheep were equally and randomly divided into Groups 1-4, fed with diets containing 0, 5, 10, and 20 g alfalfa saponins per kg, respectively, for 40 consecutive days. During the treatments, the body weight change was recorded for each sheep. Before, during, and after the treatments of alfalfa saponins, serum was collected from each group to compare the levels of biochemical and immune factors. All sheep were killed after the treatments, and the longissimus dorsi muscle was collected to compare the meat quality. The results validated the effects of alfalfa saponins on the growth performance and meat quality in Small-Tailed Han sheep, and the supplementation level of 10 g/kg was the best. Alfalfa saponins also had effects on the levels of biochemical factors in serum. However, both dose- and time-dependent effects were observed. After a shorter feeding period (14 days), the concentrations of cholesterol (CHOL) and low-density lipoprotein (LDL) in Groups 2, 3, and 4 were all lower than those in the control group; however, when alfalfa saponins were continuously fed, this effect was not apparent or even gone. Supplying alfalfa saponins increased serum concentrations of IgA, IgG, IgE, IgM, IL-1, IFN-α, and IFN-β. And this effect was distinctly observed in Groups 3 and 4. Based on the current results, the alfalfa saponins concentration of 10 g/kg (for 14 consecutive days) could be suggested as the optimum ratio for good health conditions of Small-Tailed Han sheep.
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http://dx.doi.org/10.3389/fvets.2022.924373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353124PMC
July 2022

The Temporal Lagged Relationship Between Meteorological Factors and Scrub Typhus With the Distributed Lag Non-linear Model in Rural Southwest China.

Front Public Health 2022 22;10:926641. Epub 2022 Jul 22.

West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

Background: Meteorological factors can affect the emergence of scrub typhus for a period lasting days to weeks after their occurrence. Furthermore, the relationship between meteorological factors and scrub typhus is complicated because of lagged and non-linear patterns. Investigating the lagged correlation patterns between meteorological variables and scrub typhus may promote an understanding of this association and be beneficial for preventing disease outbreaks.

Methods: We extracted data on scrub typhus cases in rural areas of Panzhihua in Southwest China every week from 2008 to 2017 from the China Information System for Disease Control and Prevention. The distributed lag non-linear model (DLNM) was used to study the temporal lagged correlation between weekly meteorological factors and weekly scrub typhus.

Results: There were obvious lagged associations between some weather factors (rainfall, relative humidity, and air temperature) and scrub typhus with the same overall effect trend, an inverse-U shape; moreover, different meteorological factors had different significant delayed contributions compared with reference values in many cases. In addition, at the same lag time, the relative risk increased with the increase of exposure level for all weather variables when presenting a positive association.

Conclusions: The results found that different meteorological factors have different patterns and magnitudes for the lagged correlation between weather factors and scrub typhus. The lag shape and association for meteorological information is applicable for developing an early warning system for scrub typhus.
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http://dx.doi.org/10.3389/fpubh.2022.926641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355273PMC
August 2022

Recent progress on covalent organic framework materials as CO reduction electrocatalysts.

Front Chem 2022 22;10:942492. Epub 2022 Jul 22.

Jiangsu Engineering and Technology Research Center of VOCs Treatment, Environmental Engineering College, Nanjing Polytechnic Institute, Nanjing, JS, China.

CO emission caused by fuel combustion and human activity has caused severe climate change and other subsequent pollutions around the world. Carbon neutralization various novel technologies to alleviate the CO level in the atmosphere has thus become one of the major topics in modern research field. These advanced technologies cover CO capture, storage and conversion, ., and electrocatalytic CO reduction reaction (CORR) by heterogeneous catalysts is among the most promising methods since it could utilize renewable energy and generate valuable fuels and chemicals. Covalent organic frameworks (COFs) represent crystalline organic polymers with highly rigid, conjugated structures and tunable porosity, which exhibit significant potential as heterogeneous electrocatalysts for CORR. This review briefly introduces related pioneering works in COF-based materials for electrocatalytic CORR in recent years and provides a basis for future design and synthesis of highly active and selective COF-based electrocatalysts in this direction.
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http://dx.doi.org/10.3389/fchem.2022.942492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355711PMC
July 2022

Hexavalent Chromium Exposure Induces Intestinal Barrier Damage Activation of the NF-κB Signaling Pathway and NLRP3 Inflammasome in Ducks.

Front Immunol 2022 22;13:952639. Epub 2022 Jul 22.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China.

Hexavalent chromium [Cr(VI)] is a dangerous heavy metal which can impair the gastrointestinal system in various species; however, the processes behind Cr(VI)-induced intestinal barrier damage are unknown. Forty-eight healthy 1-day-old ducks were stochastically assigned to four groups and fed a basal ration containing various Cr(VI) dosages for 49 days. Results of the study suggested that Cr(VI) exposure could significantly increase the content of Cr(VI) in the jejunum, increase the level of diamine oxidase (DAO) in serum, affect the production performance, cause histological abnormalities (shortening of the intestinal villi, deepening of the crypt depth, reduction and fragmentation of microvilli) and significantly reduced the mRNA levels of intestinal barrier-related genes (ZO-1, occludin, claudin-1, and MUC2) and protein levels of ZO-1, occludin, cand laudin-1, resulting in intestinal barrier damage. Furthermore, Cr(VI) intake could increase the contents of hydrogen peroxide (HO) and malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18) but decrease the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione reductase (GR), as well as up-regulate the mRNA levels of TLR4, MyD88, NF-κB, TNFα, IL-6, NLRP3, caspase-1, ASC, IL-1β, and IL-18 and protein levels of TLR4, MyD88, NF-κB, NLRP3, caspase-1, ASC, IL-1β, and IL-18 in the jejunum. In conclusion, Cr(VI) could cause intestinal oxidative damage and inflammation in duck jejunum by activating the NF-κB signaling pathway and the NLRP3 inflammasome.
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http://dx.doi.org/10.3389/fimmu.2022.952639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353580PMC
August 2022

Accuracy Evaluation of Carotid-Femoral Pulse Wave Velocity Estimated by Smart Terminal Watch.

Front Cardiovasc Med 2022 22;9:893557. Epub 2022 Jul 22.

Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

To evaluate the accuracy of the smartwatch in estimating carotid-femoral pulse wave velocity (cfPWV). A cohort of gender-matched volunteers aged 18-80 years were recruited. At the sitting and supine positions, cfPWV was measured alternately by smartwatch and CompliorAnalyse, for each participant, and nine sets of data were collected from each participant with a 60 s interval between measurements. The accuracy of cfPWV measurement for smartwatches was assessed using mean error (ME) and mean absolute error (MAE), while the consistency of the two methods was assessed using the Bland-Altman analysis and concordance class correlation. A total of 347 participants were enrolled. The mean cfPWV was 9.01 ± 2.29 m/s measured by CompliorAnalyse and 9.06 ± 1.94 m/s by smartwatch. The consistency correlation coefficient (CCC) was 0.9045 (95% CI 0.8853-0.9206), the ME was 0.046 ± 0.92, and the MAE was 0.66 (95% CI 0.59-0.73). Bland-Altman analysis showed that the error of 95% samples was in the range between -1.77 m/s and 1.86 m/s. The Kappa value of cfPWV greater than 10 m/s was 0.79, the area under the ROC curve was 0.97 ( < 0.001), sensitivity was 0.90, specificity was 0.93, positive predictive value was 0.83 and negative predictive value was 0.96. Smartwatch can accurately estimate cfPWV to evaluate arterial stiffness. This method is simple and feasible and is suitable for people to actively and early monitor vascular elasticity.
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http://dx.doi.org/10.3389/fcvm.2022.893557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353553PMC
July 2022

Formation of Microfibrillar PBAT in PGA Films: An Effective Way to Robust Barrier and Mechanical Properties for Fully Biodegradable Packaging Films.

ACS Omega 2022 Jun 10;7(24):21280-21290. Epub 2022 Jun 10.

Beijing Key Laboratory of Quality Evaluation Technology for Hygiene and Safety of Plastics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, China.

Poly(glycolic acid) (PGA) is a semicrystalline biodegradable polyester with high gas barrier properties. However, due to its poor processability and low ductility, PGA could hardly find applications in the packaging field. Here, a strategy was adopted for generation of high-aspect-ratio flexible microfibrils with strong interface affinity for the PGA matrix. Because poly(butylene adipate--terephthalate) (PBAT) possesses impressive ductility, it was selected as the "fibrillar toughening phase" to enhance the ductility of PGA. Moreover, a chain extender was used to enhance the interfacial adhesion between the two polymers. The extrusion blown film technique was then used to develop fully biodegradable PGA/PBAT films with a superior combination of excellent barrier performance and robust mechanical properties. The PBAT phase can form microfibrils under the influence of extensional flow. Simultaneously, the synergetic function of the extensional flow field could effectively promote the motion of the PGA molecular chain to develop an oriented crystalline microstructure. Because of the aligned oriented lamellar crystal of PGA and oriented PBAT fibril structures serving as robust "barrier walls" 60PGA/ADR blown films demonstrated dramatically improved resistance to oxygen and water vapor, with 59 and 44 times lower oxygen permeability and water vapor permeability, respectively, when compared to the neat PBAT blown film. As a result, PGA/PBAT blown films offer a variety of benefits, including superior ductility, toughness, and a strong gas barrier property. The potential of these films to degrade makes them a viable contender for replacing classical nondegradable packing films.
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http://dx.doi.org/10.1021/acsomega.2c02484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348010PMC
June 2022

Opportunistic osteoporosis screening using chest CT with artificial intelligence.

Osteoporos Int 2022 Aug 6. Epub 2022 Aug 6.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, Hubei Province, China.

Osteoporosis has a high incidence and a low detection rate. If it is not detected in time, it will cause osteoporotic fracture and other serious consequences. This study showed that the attenuation values of vertebrae on chest CT could be used for opportunistic screening of osteoporosis. This will be beneficial to improve the detection rate of osteoporosis and reduce the incidence of adverse events caused by osteoporosis.

Introduction: To explore the value of the attenuation values of all thoracic vertebrae and the first lumbar vertebra measured by artificial intelligence on non-enhanced chest CT to do osteoporosis screening.

Methods: On base of images of chest CT, using artificial intelligence (AI) to measure the attenuation values (HU) of all thoracic and the first vertebrae of patients who underwent CT examination for lung cancer screening and dual-energy X-ray absorptiometry (DXA) examination during the same period. The patients were divided into three groups: normal group, osteopenia group, and osteoporosis group according to the results of DXA. Clinical baseline data and attenuation values were compared among the three groups. The correlation between attenuation values and BMD values was analyzed, and the predictive ability and diagnostic efficacy of attenuation values of thoracic and first lumbar vertebrae on osteopenia or osteoporosis risk were further evaluated.

Results: CT values of each thoracic vertebrae and the first lumbar vertebrae decreased with age, especially in menopausal women and presented high predictive ability and diagnostic efficacy for osteopenia or osteoporosis. After clinical data correction, with every 10 HU increase of CT values, the risk of osteopenia or osteoporosis decreased by 32 ~ 44% and 61 ~ 80%, respectively. And the combined diagnostic efficacy of all thoracic vertebrae was higher than that of a single vertebra. The AUC of recognizing osteopenia or osteoporosis from normal group was 0.831and 0.972, respectively.

Conclusions: The routine chest CT with AI is of great value in opportunistic screening for osteopenia or osteoporosis, which can quickly screen the population at high risk of osteoporosis without increasing radiation dose, thus reducing the incidence of osteoporotic fracture.
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http://dx.doi.org/10.1007/s00198-022-06491-yDOI Listing
August 2022

Selective removal of Hg(II) by UiO-66-NH modified by 4-quinolinecarboxaldehyde: from experiment to mechanism.

Environ Sci Pollut Res Int 2022 Aug 5. Epub 2022 Aug 5.

Yunnan Institute of Product Quality Supervision & Inspection, Kunming, 650093, Yunnan, China.

In wastewater, heavy metal Hg causes serious harm to ecology, so it needs to be removed. In this paper, a novel MOF adsorbent (UiO-66-QU) was prepared by modifying UiO-66-NH with 4-quinolinecarboxaldehyde, which was used to selectively remove Hg(II) from water. The adsorbent was characterized using Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), zeta potentiometer, and X-ray photoelectron spectroscopy (XPS). In order to investigate the Hg(II) adsorption performance of UiO-66-QU, the effect of time, initial concentration, pH, and temperature were carried out. Langmuir model fitting shows that the maximum adsorption capacity of UiO-66-QU for Hg(II) is 556 mg/g at 298 K. The experimental results show that UiO-66-QU has better Hg(II) adsorption capacity than UiO-66-NH. The isotherm is in accordance with pseudo-second-order models. It is indicated that the adsorption process is mainly monolayer chemical adsorption. The thermodynamic parameters also indicate that the adsorption process is spontaneous and endothermic. It has excellent reusability and selectivity. XPS and the zeta potential showed that the adsorption mechanism was the complex reaction of Hg(II) with nitrogenous group. Therefore, the adsorbent has potential application prospects in removal of Hg(II) from wastewater.
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http://dx.doi.org/10.1007/s11356-022-22276-6DOI Listing
August 2022

A Hierarchical Si/C Nanocomposite of Stable Conductive Network Formed Through Thermal Phase Separation of Asphaltenes for High-Performance Li-Ion Batteries.

Small 2022 Aug 5:e2203102. Epub 2022 Aug 5.

Department of Materials Science and Engineering, Shenzhen Key Laboratory of Interfacial Science and Engineering of Materials, Key University Laboratory of Highly Efficient Utilization of Solar Energy and Sustainable Development, Southern University of Science and Technology, Shenzhen, 518055, P. R. China.

Silicon is one of the most promising anode materials for lithium-ion batteries. However, the huge volume change of silicon during lithiation/delithiation triggers continuous growth of solid-electrolyte interphase, loss of conductive contacts and structural collapse of the electrode, which causes a rapid deterioration of battery capacities. Inspired by the polyaromatic molecular nature and phase separation of asphaltenes in bitumen during thermal cracking, a hierarchical Si/C nanocomposite of robust carbon coatings and a firmly connected carbon framework on the silicon surface is synthesized by controlling the concentration of asphaltenes as carbon source and hence desired phase separation during the subsequent carbonization. The electrode made using this special Si/C nanocomposite exhibits a high reversible capacity of 1149 mAh g after 600 cycles with a capacity retention of 98.5% and the operation ability at a high mass loading over 10 mg cm or an area capacity of 23.8 mAh cm , which represents one of the highest area capacities reported in open literature but with much more stable and prolonged operations. This simple and efficient strategy is easy to scale up for commercial production to meet the rapid growth of the electric vehicle industry.
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http://dx.doi.org/10.1002/smll.202203102DOI Listing
August 2022

Inflammation down regulates stromal cell-derived factor 1α in the early phase of pulpitis.

Cytokine 2022 Aug 2;158:155983. Epub 2022 Aug 2.

Department of Operative Dentistry and Endodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

The key to prevent pulp necrosis in the early stage of pulpitis is to promote tissue repair, which begins with cell migration. Stromal cell-derived factor 1α (SDF-1α) has been proven to promote cell migration. Related research has so far concentrated on the biological effects of SDF-1α while its expression in pulpitis is still unclear. We investigated the effect of inflammation on SDF-1α in dental pulp and the underlying regulatory mechanisms. First, rat pulpitis models were established by exposing pulp. SDF-1α was decreased on the 3rd day but increased on the 7th day. Next, lipopolysaccharide from Porphyromonas gingivalis (Pg.LPS) was applied to dental pulp cells (DPCs). Within 24 h, SDF-1α decreased, but after 48 h, it steadily increased. Similarly, SDF-1α expression in human chronic pulpitis tissues was also increased. To investigate the effect of altered SDF-1α on DPC migration, cell supernatants collected following Pg.LPS treatment were utilized to stimulate DPCs, and the number of migrated cells was correlated with changes in SDF-1α secretion. Finally, we explored the regulatory mechanisms of SDF-1α down-regulation in the early phase of pulpitis. Within 24 h, JNK/c-Jun pathway was activated in DPC inflammation. When JNK pathway was suppressed, SDF-1α rose. Furthermore, tumor necrosis factor receptor 2 (TNFR2) and apoptosis signal-regulated kinase-interacting protein 1 (AIP1) were up-regulated. Knockdown of them abolished Pg.LPS-induced activation of JNK and c-Jun(Ser63) and significantly enhanced SDF-1α. Our findings indicated that in the early phase of pulpitis, inflammation suppressed SDF-1α by up-regulating TNFR2 and AIP1, which activated JNK/c-Jun(Ser63) pathway.
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http://dx.doi.org/10.1016/j.cyto.2022.155983DOI Listing
August 2022

Silencing of COL3A1 represses proliferation, migration, invasion, and immune escape of triple negative breast cancer cells via down-regulating PD-L1 expression.

Cell Biol Int 2022 Aug 5. Epub 2022 Aug 5.

Department of Breast Surgery, Fuzhou First Hospital Affiliated to Fujian Medical University, Fuzhou, China.

This study is designed to illuminate the specific role and underlying mechanism of collagen type III alpha 1 chain (COL3A1) in triple negative breast cancer (TNBC). Quantitative real-time polymerase chain reaction was applied to examine mRNA expression of COL3A1. Western blot analysis was employed to determine protein levels of COL3A1, programmed death ligand 1 (PD-L1), Bcl-2, and cleaved caspase-3. Immunohistochemistry staining was utilized for assessing protein expression of Ki67 and COL3A1 in tissues. The proliferous capacity of cells was assessed through CCK-8 assay and 5-Ethynyl-2'-deoxyuridine assay. Cell apoptosis and the percentage of CD8 T cells were measured using flow cytometry. Migration and invasion of TNBC cells were examined via transwell assay. Lactate dehydrogenase (LDH) release was measured via a LDH assay kit. For establishing a xenograft tumor model, MDA-MB-231 cells were injected into the flank of mice through subcutaneous injection. COL3A1 expression was raised in TNBC tissues and cells, and it was inversely associated with overall survival data of TNBC patients. COL3A1 downregulation repressed proliferation, invasion, migration, and immune escape of TNBC cells along with tumor growth of xenograft mice. In TNBC cells and tumor tissues of mice, protein expression of PD-L1 was reduced by COL3A1 knockdown. COL3A1 knockdown-mediated inhibitory effects on cell proliferation, migration, invasion, and immune escape were reversed by PD-L1 upregulation in vitro. Silencing of COL3A1 exerted an antitumor role in TNBC, implying its potential as a therapeutic target for TNBC.
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http://dx.doi.org/10.1002/cbin.11875DOI Listing
August 2022

LncRNA-412.25 activates the LIF/STAT3 signaling pathway in ovarian granulosa cells of Hu sheep by sponging miR-346.

FASEB J 2022 Sep;36(9):e22467

Hu Sheep Academy, Nanjing Agricultural University, Nanjing, China.

Although long non-coding RNAs (lncRNAs) are reported to regulate follicular development and reproductive disease pathogenesis, the underlying mechanisms have not been elucidated. In this study, lncRNA expression profiling of different-sized healthy follicles from Hu sheep with different prolificacy revealed 50 613 lncRNAs. Numerous lncRNAs were differentially expressed among different comparison groups. This study characterized one novel transcript, lncRNA-412.25 (from healthy follicles with a diameter of >5 mm), which was predominantly expressed in the high prolificacy group and localized to the cytoplasm of granulosa cells (GCs). LncRNA-412.25 knockdown promoted and inhibited Hu sheep GC apoptosis and proliferation, respectively. Interestingly, lncRNA-412.25 could directly bind to miR-346, which can target the gene of leukemia inhibitory factor (LIF). Knockdown of lncRNA-412.25 promoted GC apoptosis by downregulating LIF expression, where this effect was attenuated by miR-346. Moreover, the miR-346 inhibitor mitigated the lncRNA-412.25 knockdown-induced downregulation of phosphorylated protein of signal transducer and activator of transcription 3 (STAT3), which was validated using immunofluorescence analysis. Our results demonstrated that lncRNA-412.25 regulates GC proliferation and apoptosis in Hu sheep by binding to miR-346 and then activating the LIF/STAT3 pathway. These findings provide novel insights into the mechanisms underlying prolificacy in sheep.
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http://dx.doi.org/10.1096/fj.202200632RDOI Listing
September 2022

Combining PET with MRI to improve predictions of progression from mild cognitive impairment to Alzheimer's disease: an exploratory radiomic analysis study.

Ann Transl Med 2022 May;10(9):513

Department of Nuclear Medicine, University Hospital Bern, Bern, Switzerland.

Background: This study aimed to explore the potential of a combination of 18F-fluorodeoxyglucose positron emission tomography (F-FDG PET) and magnetic resonance imaging (MRI) to improve predictions of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). The predictive performances and specific associated biomarkers of these imaging techniques used alone (single-modality imaging) and in combination (dual-modality imaging) were compared.

Methods: This study enrolled 377 patients with MCI and 94 healthy control participants from 2 medical centers. Enrolment was based on the patients' brain MRI and PET images. Radiomic analysis was performed to evaluate the predictive performance of dual-modality F-FDG PET and MRI scans. Regions of interest (ROIs) were determined using an a priori brain atlas. Radiomic features in these ROIs were extracted from the MRI and F-FDG PET scan data. These features were either concatenated or used separately to select features and construct Cox regression models for prediction in each modality. Harrell's concordance index (C-index) was then used to assess the predictive accuracies of the resulting models, and correlations between the MRI and F-FDG PET features were evaluated.

Results: The C-indices for the two test datasets were 0.77 and 0.80 for dual-modality F-FDG PET/MRI, 0.75 and 0.73 for single-modality F-FDG PET, and 0.74 and 0.76 for single-modality MRI. In addition, there was a significant correlation between the crucial image signatures of the different modalities.

Conclusions: These results indicate the value of imaging features in monitoring the progress of MCI in populations at high risk of developing AD. However, the incremental benefit of combining F-FDG PET and MRI is limited, and radiomic analysis of a single modality may yield acceptable predictive results.
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http://dx.doi.org/10.21037/atm-21-4349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347042PMC
May 2022

Light Emitting Diodes Irradiation Regulates miRNA-877-3p to Promote Cardiomyocyte Proliferation.

Int J Med Sci 2022 11;19(8):1254-1264. Epub 2022 Jul 11.

Department of Laboratory Medicine at the Fourth Affiliated Hospital, and Department of Pharmacy at the Second Affiliated Hospital, Harbin Medical University, Harbin, China.

Mammalian cardiomyocytes (CMs) maintain a low capacity for self-renewal in adulthood, therefore the induction of CMs cycle re-entry is an important approach to promote myocardial repair after injury. Recently, photobiomodulation (PBM) has been used to manipulate physiological activities of various tissues and organs by non-invasive means. Here, we demonstrate that conditioned PBM using light-emitting diodes with a wavelength of 630 nm (LED-Red) was capable of promoting the proliferation of neonatal CMs. Further studies showed that low-power LED-Red affected the expression of miR-877-3p and promoted the proliferation of CMs. In contrast, silencing of miR-877-3p partially abolished the pro-proliferative actions of LED-Red irradiation on CMs. Mechanistically, GADD45g was identified as a downstream target gene of miR-877-3p. Conditioned LED-Red irradiation also inhibited the expression of GADD45g in neonatal CMs. Moreover, GADD45g siRNA reversed the positive effect of LED-Red on the proliferation of neonatal CMs. Taken together, conditioned LED-Red irradiation increased miR-877-3p expression and promoted the proliferation of neonatal CMs by targeting GADD45g. This finding provides a new insight into the role of LED-Red irradiation in neonatal CMs biology and suggests its potential application in myocardial injury repair.
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http://dx.doi.org/10.7150/ijms.70743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346386PMC
August 2022

Research Progress in the Medical Application of Heavy Water, Especially in the Field of DO-Raman Spectroscopy.

Int J Med Sci 2022 18;19(8):1357-1363. Epub 2022 Jul 18.

Department of Breast Surgery, First Hospital of Jilin University, Changchun, Jilin 130021.

Heavy water is an ideal contrast agent for metabolic activity and can be adapted to a wide range of biological systems owing to its non-invasiveness, universal applicability, and cost-effectiveness. As a new type of probe, the heavy isotope of water has been widely used in the study of cell development, metabolism, tissue homeostasis, aging, and tumor heterogeneity. Herein, we review findings supporting the applications of and research on heavy water in monitoring of bacterial metabolism, rapid detection of drug sensitivity, identification of tumor cells, precision medicine, and evaluation of skin barrier function and promote the use of heavy water as a suitable marker for the development of detection and treatment methodologies.
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http://dx.doi.org/10.7150/ijms.73150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346379PMC
August 2022

Biochar addition regulates soil phosphorus fractions and improves release of available phosphorus under freezing-thawing cycles.

Sci Total Environ 2022 Aug 1:157748. Epub 2022 Aug 1.

School of Water Conservancy and Civil Engineering, Northeast Agricultural University, Harbin 150030, China; Joint Laboratory of Northeast Agricultural University and Max Planck Institute of Colloids and Interfaces (NEAU-MPICI), Harbin 150030, China. Electronic address:

Currently, the shortage of phosphorus resources is becoming more and more serious. In general, phosphorus fertilizer is poorly utilized in soil and tends to gradually accumulate. Freezing-thawing cycles (FT) are seasonal phenomenon occurring in high latitudes and altitudes regions, which have obvious influence on the form of phosphorus in soil. This study investigates the effect of biochar on soil physicochemical properties, phosphorus form and availability under FT and thermostatic incubation (TH) condition. Compared with treatment without biochar, 4 % biochar addition increased the soil pH value, electrical conductivity, organic matter and Olsen-P of soil by a maximum of 0.76, 285.55 μS/cm, 28.60 g/kg and 139.27 mg/kg, respectively. Moreover, according to Hedley-P classification results, under FT condition, the content of labile phosphorus pool is always greater than those under TH. FT may promote the conversion of phosphorus from other fractions to labile phosphorus pools. Redundancy analysis results show that biochar addition and FT can not only directly change the soil phosphorus pool, but also alter the soil physicochemical properties and microbial community, which further affect the adsorption and mineralization of phosphorus in soil. The results of this study will be devoted to understanding the changes in soil phosphorus fractions under the effects of biochar addition and FT, providing references for agricultural production in areas where FT occur.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157748DOI Listing
August 2022

Carbon Nanotubes/Polydopamine/ZSM-5 Composite Soil Conditioner with Good Controlled Release and Adsorption Properties.

Langmuir 2022 Aug 4. Epub 2022 Aug 4.

Jiangsu LuHong Landscaping Engineering Company Limited, Jiangsu 226100, P. R. China.

Currently, the excessive application of fertilizers and the random discharge of waste water, waste gas, and residues have led to more and more serious soil pollution problems. Zeolite is the most promising material for preparing a green and environmentally friendly soil conditioner. Herein, the carbon nanotubes/polydopamine/ZSM-5 composite soil conditioner was prepared by a facile two-step method, and it was used to release fulvic acid and adsorb methylene blue to improve the environment. The cumulative release rate of the composite soil conditioner was 52% within 430 h for fulvic acid, which had a good sustained release effect and could be sustained-released in different acid-based surroundings. In addition, it showed a good adsorption capacity of methylene blue, and it is about 80.02 mg/g which was about six times higher than that of ZSM-5. It was beneficial for the adsorption of methylene blue in a neutral environment. Finally, it could promote the growth of brassica chinensis and maize, and the promotion effect was 60 and 35%, respectively. Therefore, the carbon nanotubes/polydopamine/ZSM-5 composite soil conditioner is a green and efficient material, which provides a new strategy to solve the problem of soil pollution.
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http://dx.doi.org/10.1021/acs.langmuir.2c01175DOI Listing
August 2022

A druggable UHRF1/DNMT1/GLI complex regulates Sonic hedgehog dependent tumor growth.

Mol Cancer Res 2022 Aug 4. Epub 2022 Aug 4.

Georgetown University, Washington, DC, United States.

Dysregulation of Sonic hedgehog (SHH) signaling drives the growth of distinct cancer subtypes, including medulloblastoma (MB). Such cancers have been treated in the clinic with a number of clinically relevant SHH inhibitors, the majority of which target the upstream SHH regulator, Smoothened (SMO). Despite considerable efficacy, many of these patients develop resistance to these drugs, primarily due to mutations in SMO. Therefore, it is essential to identify druggable, signaling components downstream of SMO to target in SMO inhibitor resistant cancers. We utilized an integrated functional genomics approach to identify epigenetic regulators of SHH- signaling and identified a novel complex of Ubiquitin-like with PHD and RING finger domains 1 (UHRF1), DNA methyltransferase 1 (DNMT1), and GLI proteins. We show that this complex is distinct from previously described UHRF1/DNMT1 complexes, suggesting that it works in concert to regulate GLI activity in SHH driven tumors. Importantly, we show that UHRF1/DNMT1/GLI complex stability is targeted by a repurposed FDA-approved therapy, with a subsequent reduction in the growth of SHH-dependent MB ex vivo and in vivo. Implications: This work describes a novel, druggable UHRF1/DNMT1/GLI complex that regulates SHH-dependent tumor growth, and highlights an FDA-approved drug capable of disrupting this complex to attenuate tumor growth.
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http://dx.doi.org/10.1158/1541-7786.MCR-22-0182DOI Listing
August 2022

Oral eltanexor treatment of patients with higher-risk myelodysplastic syndrome refractory to hypomethylating agents.

J Hematol Oncol 2022 Aug 3;15(1):103. Epub 2022 Aug 3.

West Virginia University Cancer Institute, Wheeling Hospital, Wheeling, WV, USA.

Patients with higher-risk myelodysplastic syndromes (MDS) refractory to hypomethylating agents (HMAs) have limited therapeutic options and an expected overall survival (OS) of 3-5 months. Eltanexor is an investigational oral selective inhibitor of nuclear export with low central nervous system penetrance and an acceptable tolerability profile. Preclinical studies suggest that myeloid malignancies are sensitive to nuclear export inhibition. Eltanexor exhibited efficacy in hematologic models, supporting exploration in a clinical trial. This phase 1/2 study (NCT02649790) assessed single-agent activity of eltanexor in patients with higher-risk MDS and 5-19% myeloblasts. Two starting doses of eltanexor were evaluated: 20 mg (n = 15), 10 mg (n = 5), both administered on days 1-5 each week of a 28-day cycle. Twenty patients with primary HMA-refractory MDS, with a median age of 77 years (range 62-89), and a median of two prior treatment regimens (range 1-4) were enrolled. Of these, 15 were evaluated for efficacy and 20 for safety. The overall response rate (ORR) was 53.3%, with seven patients (46.7%) achieving marrow complete remission (mCR) and one additional patient achieving hematologic improvement (HI). In the 10 mg group, three patients (60%) reached mCR and two (40%) stable disease (SD), while for 20 mg, four patients (40%) had mCR and two (20%) SD. A total of three patients (20%) had HI and became transfusion independent ≥ 8 weeks. Median OS for the efficacy-evaluable patients (n = 15) was 9.86 months (7.98, NE). Overall, the most frequently reported treatment-related adverse events were nausea (45%), diarrhea (35%), decreased appetite (35%), fatigue and neutropenia (both 30%). Single-agent oral eltanexor was active, safe, and well tolerated in patients with higher-risk, primary HMA-refractory MDS.
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http://dx.doi.org/10.1186/s13045-022-01319-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351096PMC
August 2022

Rapid emergence of a PB2 D701N substitution during adaptation of an H9N2 avian influenza virus in mice.

Arch Virol 2022 Aug 3. Epub 2022 Aug 3.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, and National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.

H9N2 avian influenza viruses (AIVs) have been isolated frequently from multiple avian species and, occasionally, from humans. To explore the potential molecular basis of cross-species transmission of H9N2 AIVs, an H9N2 AIV (A/chicken/Zhejiang/221/2016) was serially passaged in mouse lung. The results showed that the mouse-adapted H9N2 virus exhibited higher virulence and replicated more efficiently in mouse lung and liver. Whole-genome sequencing showed an amino acid substitution, D701N, in the PB2 protein, which is likely associated with the increased replicative ability of H9N2 virus in mice. The rapid emergence of adaptive substitutions indicates the necessity of continuous monitoring of H9N2 virus in poultry.
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http://dx.doi.org/10.1007/s00705-022-05536-1DOI Listing
August 2022

TOLLIP-mediated autophagic degradation pathway links the VCP-TMEM63A-DERL1 signaling axis to triple-negative breast cancer progression.

Autophagy 2022 Aug 3:1-17. Epub 2022 Aug 3.

Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai Yangpu, China.

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat due to the lack of effective targeted therapies. Transmembrane (TMEM) proteins represent attractive drug targets for cancer therapy, but biological functions of most members of the TMEM family remain unknown. Here, we report for the first time that TMEM63A (transmembrane protein 63A), a poorly characterized TMEM protein with unknown functions in human cancer, functions as a novel oncogene to promote TNBC cell proliferation, migration, and invasion and xenograft tumor growth and lung metastasis . Mechanistic investigations revealed that TMEM63A localizes in endoplasmic reticulum (ER) and lysosome membranes, and interacts with VCP (valosin-containing protein) and its cofactor DERL1 (derlin 1). Furthermore, TMEM63A undergoes autophagy receptor TOLLIP-mediated autophagic degradation and is stabilized by VCP through blocking its lysosomal degradation. Strikingly, TMEM63A in turn stabilizes oncoprotein DERL1 through preventing TOLLIP-mediated autophagic degradation. Notably, pharmacological inhibition of VCP by CB-5083 or knockdown of DERL1 partially abolishes the oncogenic effects of TMEM63A on TNBC progression both and . Collectively, these findings uncover a previously unknown functional and mechanistic role for TMEM63A in TNBC progression and provide a new clue for targeting TMEM63A-driven TNBC tumors by using a VCP inhibitor. ATG16L1, autophagy related 16 like 1; ATG5, autophagy related 5; ATP5F1B/ATP5B, ATP synthase F1 subunit beta; Baf-A1, bafilomycin A; CALCOCO2/NDP52, calcium binding and coiled-coil domain 2; CANX, calnexin; DERL1, derlin 1; EGFR, epidermal growth factor receptor; ER, endoplasmic reticulum; ERAD, endoplasmic reticulum-associated degradation; HSPA8, heat shock protein family A (Hsp70) member 8; IP, immunoprecipitation; LAMP2A, lysosomal associated membrane protein 2; NBR1, NBR1 autophagy cargo receptor; OPTN, optineurin; RT-qPCR, reverse transcription-quantitative PCR; SQSTM1/p62, sequestosome 1; TAX1BP1, Tax1 binding protein 1; TMEM63A, transmembrane protein 63A; TNBC, triple-negative breast cancer; TOLLIP, toll interacting protein; VCP, valosin containing protein.
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http://dx.doi.org/10.1080/15548627.2022.2103992DOI Listing
August 2022
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