Publications by authors named "Bo Feng"

747 Publications

Understanding the Association between Online Social Support Obtainment and Coping during a Public Crisis.

J Health Commun 2022 Aug 5:1-10. Epub 2022 Aug 5.

School of Journalism and Communication, Renmin University of China, Beijing, China.

This study aims to examine how the process of online support obtainment may affect cognitive and behavioral coping during a public crisis. A cross-sectional online survey ( = 555) was conducted during the early stage of the COVID-19 pandemic in the U.S. Our findings revealed that informational support, obtained primarily through passive and private online involvement, led to increased risk perceptions of COVID-19; emotional support, obtained mainly via private online involvement, appeared to elicit higher perceived efficacy to cope with the crisis. People's engagement in preventive behaviors was found to be affected by efficacy perceptions, but not by risk perceptions. The results suggested that online social support functioned as a double-edged sword to affect people's coping with a public crisis.
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http://dx.doi.org/10.1080/10810730.2022.2107738DOI Listing
August 2022

Micro/nano-topography promotes osteogenic differentiation of bone marrow stem cells by regulating periostin expression.

Colloids Surf B Biointerfaces 2022 Jul 16;218:112700. Epub 2022 Jul 16.

School of Materials Science & Engineering, Southwest Jiaotong University, Chengdu 610031, China; College of Medicine, Southwest Jiaotong University, Chengdu 610031, China. Electronic address:

Micro/nano-topography (MNT) is an important factor affecting cell response. Earlier studies using titania (TiO) nanotube as a model of MNT found that they mediated the differentiation of BMSCs into osteoblasts, but the mechanisms are not fully understood. Surprisingly, Periostin (Postn), a secreted protein involved in extracellular matrix (ECM) construction and promoting osteogenic differentiation of bone marrow stem cells (BMSCs), was previously observed to significantly up-regulated on TiO nanotube. We proposed that Postn may act as a MNT signal transduction role. In this study, we investigated the effect of MNT on Postn, and the influence of Postn on osteogenic differentiation-related genes through focal adhesion and downstream signals. It was found that, titanium (Ti) plates carrying TiO nanotubes with diameters of ∼100 nm (TNT-100) significantly up-regulated the expression of Postn compared with flat Ti. Furthermore, Postn activated the downstream focal adhesion kinase (FAK) signal pathway and β-catenin into the nucleus by interacting with integrin αV. Surprisingly, TNT-100 up-regulated the transcription level of Wnt3a, which was independent of the up-regulation of Postn. This new Postn signaling pathway may provide more insights into the signal transduction mechanism of MNT and development of biomaterials with improved osteogenic properties.
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http://dx.doi.org/10.1016/j.colsurfb.2022.112700DOI Listing
July 2022

Imaging features, staging system, and surgical management of giant cell lesions of the temporal bone.

Acta Otolaryngol 2022 Jul 25:1-9. Epub 2022 Jul 25.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, National Clinical Research Center for Otolaryngologic Diseases, Key Lab of Hearing Impairment Science of Ministry of Education, Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China.

Background: Giant cell tumors (GCTs) and giant cell granulomas (GCGs) are giant cell-rich lesions that occur extremely rarely in the temporal bone and have similar clinical presentations.

Objectives: We aimed to analyze the clinical features and introduce our staging system and surgical treatment.

Methods: Forty-six patients pathologically diagnosed with a giant cell lesion involving the temporal bone between October 2001 and October 2020 were reviewed retrospectively. The clinical characteristics, surgical approaches, and risk factors for recurrence were analyzed.

Results: GCTs and GCGs presented as masses centered on the temporomandibular joint with similar imaging features, including a thin, calcified shell and central scattered calcifications on a computed tomography scan. Differences were detected on magnetic resonance imaging in 29.6% (4/14) of GCG and 50% (16/32) of GCT cases; the remaining cases were not distinguishable. Based on our staging system and surgical strategy, 31.8% (7/22) of GCT and 10% (1/10) of GCG cases experienced recurrence, which compares to recurrence rates of 60% in GCT cases and 20% in GCG cases in previous studies.

Conclusions: Specific clinical and preoperative imaging features help to make a diagnosis of temporal giant cell-rich lesions. Our staging system and surgical strategy could help surgeons tailor the surgical strategy.
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http://dx.doi.org/10.1080/00016489.2022.2099969DOI Listing
July 2022

The adsorption mechanisms of oriental plane tree biochar toward bisphenol S: A combined thermodynamic evidence, spectroscopic analysis and theoretical calculations.

Environ Pollut 2022 Jul 20;310:119819. Epub 2022 Jul 20.

Biochar Engineering Technology Research Center of Guangdong Province, Physical Science Public Platform, School of Environmental and Chemical Engineering, Foshan University, Foshan 528000, China; Guangdong Green Technologies Co., Ltd., Foshan, 528100, China. Electronic address:

Garden pruning waste is becoming a problem that intensifies the garbage siege. It is of great significance to purify polluted water using biochar prepared from garden pruning waste. Herein, the interaction mechanism between BPS and oriental plane tree biochar (TBC) with different surface functional groups was investigated by adsorption experiments, spectroscopic analysis and theoretical calculations. Adsorption kinetics and isotherm of BPS on TBC can be satisfactorily fitted into pseudo-second-order kinetic and Langmuir models, respectively. A rapid adsorption kinetic toward BPS was achieved by TBC in 15 min. As compared with TBC prepared at low temperature (300 °C) (LTBC), the maximum adsorption capacity of TBC prepared at high temperature (600 °C) (HTBC) can be significantly improved from 46.7 mg g to 72.9 mg g. Besides, the microstructure and surface functional groups of HTBC were characterized using SEM, BET-N and XPS analysis. According to density functional theory (DFT) theoretical calculations, the higher adsorption energy of HTBC for BPS was mainly attributed to π-π interaction rather than hydrogen bonding, which was further supported by the analysis of FTIR and Raman spectra as well as the adsorption thermodynamic parameters. These findings suggested that by improving π-π interaction through high pyrolysis temperature, BPS could be removed and adsorbed by biochar with high efficacy, cost-efficiency, easy availability, and carbon-negative in nature, contributing to global carbon neutrality.
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http://dx.doi.org/10.1016/j.envpol.2022.119819DOI Listing
July 2022

The Influence of Linguistic Agency and Causality Attribution in Support-seeking about Depression on Perceived Stigma and Support Messages.

J Health Commun 2022 Jul 22:1-10. Epub 2022 Jul 22.

Department of Communication, University of California, Davis, California, USA.

This experiment examined how two language features-linguistic agency and assignment of causality-of online support-seekers' messages regarding depression influenced viewers' perceived stigma and features of their support messages. Participants (N = 254) read and responded to an online support-seeking post about depression. Our results revealed that personal stigma toward a depressed individual was lower when the individual disclosed a biological cause for the depression and assigned agency to depression than agency to human. Additionally, when agency was assigned to depression with a biological rather than non-biological cause, more positive emotion words were utilized in participants' response posts. Cognitive process words were used more often in response to messages with non-biological causality than biological causality.
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http://dx.doi.org/10.1080/10810730.2022.2104412DOI Listing
July 2022

Cyanophycin Granule Polypeptide: a Neglected High Value-Added Biopolymer, Synthesized in Activated Sludge on a Large Scale.

Appl Environ Microbiol 2022 07 7;88(14):e0074222. Epub 2022 Jul 7.

Key Laboratory of the Three Gorges Reservoir Region's Eco-Environments of MOE, Chongqing Universitygrid.190737.b, Chongqing, China.

Recovery of microbial synthetic polymers with high economic value and market demand in activated sludge has attracted extensive attention. This work analyzed the synthesis of cyanophycin granule peptide (CGP) in activated sludge and its adsorption capacity for heavy metals and dyes. The distribution and expression of synthetic genes for eight biopolymers in two wastewater treatment plants (WWTPs) were analyzed by metagenomics and metatranscriptomics. The results indicate that the abundance and expression level of CGP synthase () are similar to those of polyhydroxyalkanoate polymerase, implying high synthesis of CGP in activated sludges. CGP in activated sludge is mainly polymerized from aspartic acid and arginine, and its secondary structure is mainly β-sheet. The crude yields of CGP are as high as 104 ± 26 and 76 ± 13 mg/g dry sludge in winter and in summer, respectively, comparable to those of polyhydroxyalkanoate and alginate. CGP has a stronger adsorption capacity for anionic pollutants (Cr (VI) and methyl orange) than for cationic pollutants because it is rich in guanidine groups. This study highlights prospects for recovery and application of CGP from WWTPs. The conversion of organic pollutants into bioresources by activated sludge can reduce the carbon dioxide emission of wastewater treatment plants. Identification of new high value-added biopolymers produced by activated sludge is beneficial to recover bioresources. Cyanophycin granule polypeptide (CGP), first discovered in cyanobacteria, has unique chemical and material properties suitable for industrial food, medicine, cosmetics, water treatment, and agriculture applications. Here, we revealed for the first time that activated sludge has a remarkable ability to produce CGP. These findings could further facilitate the conversion of wastewater treatment plants into resource recycling plants.
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http://dx.doi.org/10.1128/aem.00742-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317870PMC
July 2022

Risk factors and prognostic significance of postoperative complications following lateral pelvic lymph node dissection for rectal cancer: results of the multicenter lateral node study in China.

Jpn J Clin Oncol 2022 Jul 21. Epub 2022 Jul 21.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: Total mesorectal excision (TME) plus lateral pelvic lymph node (LPN) dissection (LPND) is a technically complex and challenging procedure with higher morbidity than TME alone. We aimed to investigate the risk factors for postoperative complications after TME + LPND, and the impact of complications on patient prognosis.

Methods: A total of 387 rectal cancer patients with clinical LPN metastasis (LPNM) who underwent TME + LPND at three institutions affiliated with the Chinese Lateral Node Collaborative Group were included. Logistic regression models were used to identify the risk factors for post-surgical complications, and the log-rank test was used to compare the prognosis. Severe complications were described as grade III-V.

Results: The incidence rates of overall complications and severe complications after TME + LPND were 15.2% (59/387) and 7.8% (30/387), respectively. Multivariate analysis showed that a duration of operation ≥260 min was an independent risk factor for both overall (odds ratio [OR] = 3.03, 95% confidence interval [CI] = 1.57-5.85, P = 0.001) and severe postoperative complications (OR = 2.67, 95% CI = 1.06-6.73, P = 0.037). The development of overall postoperative complications (P = 0.114) and severe postoperative complications (P = 0.298) had no significant impact on the overall survival. However, patients with overall complications (P = 0.015) or severe complications (P = 0.031) with a postoperative hospital stay >30 days had significantly an overall worse survival.

Conclusion: A surgical duration of ≥260 min is a significant risk factor for both overall and severe postoperative complications after TME + LPND for middle-low rectal cancer. Furthermore, the development of overall complications or severe complications that require a postoperative hospital stay >30 days significantly worsens the prognosis.
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http://dx.doi.org/10.1093/jjco/hyac109DOI Listing
July 2022

Health risk assessment of groundwater nitrogen pollution in Yinchuan plain.

J Contam Hydrol 2022 May 31;249:104031. Epub 2022 May 31.

Ningxia Vocational Technical College of Industry and Commerce, Yinchuan, Ningxia 750021, China.

High nitrogen concentration of groundwater poses a threat to human health. This study evaluated the potential health risk of nitrogen pollution in Yinchuan plain by geostatistical analysis and triangular stochastic model considering different land use types, and identified the uncertainties of the parameters. 163 samples were collected from groundwater wells in different land use types. The results show that the concentration of NO-N ranges from 0.059 to 450 mg/L, with an average of 22.439 mg/L. Approximately 32% of the samples exceed Grade III threshold (20 mg/L of N). The concentration of NH-N ranges from 0.011 to 11 mg/L, with an average of 0.456 mg/L. The concentration of NO-N ranges from 0.003 to 9.09 mg/L The NO-N and NH-N concentration in the groundwater of the unutilized land use is significantly lowest among all the land types. The concentration of nitrogen is highest in farmland use. The ranking of non-carcinogenic risk under different land types for infants, children, adult males and females is: farmland use > residential land use> unutilized land use. The non-carcinogenic risk value of farmland use is three times as much as that of the residential land use. Drinking groundwater can be potentially harmful to human health, and nitrogen pollutants pose an even greater threat to infant. At the same time, considering the impact of different land use types on groundwater would avoid overestimating or underestimating regional risk value. Triangular stochastic model is more sensitive to data changes and can reduce uncertainty. The contribution rate of nitrate concentration to risk is more than 83%, indicating that random sampling is needed to improve the reliability of evaluation results. The research results of this study will provide a new way to solve the uncertainty in groundwater security management.
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http://dx.doi.org/10.1016/j.jconhyd.2022.104031DOI Listing
May 2022

Morbidity, Mortality, and Pathologic Outcomes of Transanal Versus Laparoscopic Total Mesorectal Excision for Rectal Cancer Short-term Outcomes From a Multicenter Randomized Controlled Trial.

Ann Surg 2022 Jul 11. Epub 2022 Jul 11.

Department of Colorectal Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.

Objective: To determine the morbidity, mortality, and pathologic outcomes of transanal total mesorectal resection (taTME) versus laparoscopic total mesorectal excision (laTME) among patients with rectal cancer with clinical stage I to III rectal cancer below the peritoneal reflection.

Background: Studies with sufficient numbers of patients allowing clinical acceptance of taTME for rectal cancer are lacking. Thus, we launched a randomized clinical trial to compare the safety and efficacy of taTME versus laTME.

Methods: A randomized, open-label, phase 3, noninferiority trial was performed at 16 different hospitals in 10 Chinese provinces. The primary endpoints were 3-year disease-free survival and 5-year overall survival. The morbidity and mortality within 30 days after surgery, and pathologic outcomes were compared based on a modified intention-to-treat principle; this analysis was preplanned.

Results: Between April 13, 2016, and June 1, 2021, 1115 patients were randomized 1:1 to receive taTME or laTME. After exclusion of 26 cases, modified intention-to-treat set of taTME versus laTME groups included 544 versus 545 patients. There were no significant differences between taTME and laTME groups in intraoperative complications [26 (4.8%) vs 33 (6.1%); difference, -1.3%; 95% confidence interval (CI), -4.2% to 1.7%; P=0.42], postoperative morbidity [73 (13.4%) vs 66 (12.1%); difference, 1.2%; 95% CI, -2.8% to 5.2%; P=0.53), or mortality [1 (0.2%) vs 1 (0.2%)]. Successful resection occurred in 538 (98.9%) versus 538 (98.7%) patients in taTME versus laTME groups (difference, 0.2%; 95% CI, -1.9% to 2.2%; P>0.99).

Conclusions: Experienced surgeons can safely perform taTME in selected patients with rectal cancer.
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http://dx.doi.org/10.1097/SLA.0000000000005523DOI Listing
July 2022

Metagenomics and metatranscriptomics analyses of antibiotic synthesis in activated sludge.

Environ Res 2022 Oct 22;213:113741. Epub 2022 Jun 22.

College of Environment and Resources, Xiangtan University, Xiangtan, 411105, China. Electronic address:

The generic of antibiotics is considered to be a main reason for the generation of antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs). However, little has been reported about the antibiotic biosynthesis by activated sludge. In this study, the distribution and expression of antibiotic biosynthetic genes (ABGs) in the floc sludge and biofilm from two WWTPs were deciphered using metagenomics and metatranscriptomics. The results showed that 2% of the community were in general well-linked to antibiotic production, indicating a non-negligible antibiotic synthetic ability of WWTPs. 93 ABGs belonging to 26 antibiotics were determined, among which aminoglycosides, β-lactams, ansamycins, peptides, macrolides were majority. The relative abundances of detected ABGs had a large interval, ranging from 0.000006% to 0.042%. The predominant antibiotic types of synthetic genes with higher relative expression levels were monobactams, penicillin & cephalosporins and streptomycin, primarily belonging to β-lactams and aminoglycosides. The hypothetical synthetic pathways of streptomycin synthesis and penicillin & cephalosporin synthesis were proposed. And the coexistence of ABGs and ARGs for these two antibiotics was also pronounced in activated sludge from meta-omics data. These findings for the first time demonstrated the antibiotic synthetic potential in activated sludges, revealing new sources of antibiotics and resistance genes in WWTPs, and thereby aggravating environmental pollution.
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http://dx.doi.org/10.1016/j.envres.2022.113741DOI Listing
October 2022

A Displacement Sensing Method Based on Permanent Magnet and Magnetic Flux Measurement.

Sensors (Basel) 2022 Jun 7;22(12). Epub 2022 Jun 7.

School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

This paper proposes a displacement sensing method based on magnetic flux measurement. A bridge-structured magnetic circuit, formed by permanent magnets and two ferromagnetic cores, is designed and discussed. The analyses of the equivalent magnetic circuit and three-dimensional finite element simulations showed that the magnetic flux density changes linearly with the reciprocal of the sum of a constant and the displacement. A prototype sensor of the bridge structure is developed that consists of four permanent magnets as excitation, a Hall sensor as reception, and two ferromagnetic cores as the connection. Experiments have validated the feasibility of this method. The measured results show a good linearity between the sensor's output and the reciprocal of the sum of a constant and the displacement, with a correlation coefficient greater than 0.9995 across different measurement ranges. Additionally, the measured results significantly indicate that the proposed sensor is compatible with different ferromagnetic materials with a worst-case error of less than 5%. The proposed sensor has the advantages of low cost and good linearity; however, the test object is limited to ferromagnetic materials.
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http://dx.doi.org/10.3390/s22124326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228415PMC
June 2022

Anatomic patterns and clinical significance of gastrocolic trunk of Henlé in laparoscopic right colectomy for colon cancer: Results of the HeLaRC trial.

Int J Surg 2022 Jun 17;104:106718. Epub 2022 Jun 17.

Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China. Electronic address:

Background: Recent interest in laparoscopic right colectomy with D3 lymphadenectomy for right colon cancer, has raised renewed attention to the anatomic variations of the gastrocolic trunk of Henlé (GTH). Understanding the vascular structure of the GTH region for individual patients should improve surgical outcomes. The goal of this nationwide multicenter study (Anatomical Classification of Henlé's Trunk in Laparoscopic Right Hemi-colectomy (HeLaRC) trial) was to study the anatomic patterns of the GTH region, to clarify the implications of GTH in laparoscopic right colectomy with D3 lymphadenectomy (D3-RC) and analyze their clinical significance.

Methods: We enrolled 583 patients from 26 centers across China who underwent D3-RC. The number of tributaries, length and types of GTH constitutions and their influence on intra-operative data were investigated. A nomogram score (based on the length of GTH, body mass index (BMI), tumor location, T stage and type of GTH (type I vs. non-type I) was established to assess the potential hazard of bleeding.

Results: The GTH was found in 567 patients (97.3%). The distribution of GTH types was 0 (14.1%, n = 80), I (53.3%, n = 302), II (27.0%, n = 153), III (5.6%, n = 32). Of note, the type I GTH, T1 stage and tumor location at ileocecal or ascending colon were correlated with shorter exposure time of the GTH region (P < 0.0001). Short length of GTH (P = 0.002) and tumor location (transverse colon vs. non transverse colon) (P = 0.003) were correlated with the amount of GTH bleeding during the surgery. Nomogram discrimination was good (C-index: 0.72 (95% CI: 0.64, 0.80)). The dissection plane was better in patients with type I GTH than with other types (P = 0.023).

Conclusion: GTH pattern variations may affect surgical outcomes in patients undergoing D3-RC. Better recognition of GTH anatomy might lead to a safer operation with better oncologic quality.
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http://dx.doi.org/10.1016/j.ijsu.2022.106718DOI Listing
June 2022

Short- and long-term outcomes of laparoscopic versus open selective lateral pelvic lymph node dissection for locally advanced middle-low rectal cancer: Results of a multicentre lateral node study in China.

Colorectal Dis 2022 Jun 17. Epub 2022 Jun 17.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Aim: Lateral pelvic lymph node dissection (LPND) is a technically challenging procedure, and the safety and feasibility of laparoscopic LPND remains undetermined. Here, we compared the short- and long-term survival outcomes of laparoscopic LPND with those of open LPND.

Methods: From January 2012 to December 2019, locally advanced middle-low rectal cancer patients with clinical evidence of lateral pelvic lymph node metastasis (LPNM) who underwent total mesorectal excision with LPND at three institutions were included. Propensity score matching was used to minimize selection bias. The short-term and oncological outcomes of open and laparoscopic LPND were compared.

Results: Overall, 384 patients were enrolled into the study including 277 and 107 patients who underwent laparoscopic and open LPND, respectively. After matching, patients were stratified into laparoscopic (n = 100) and open (n = 100) LPND groups. Patients in the laparoscopic LPND group had a shorter operation time (255 vs. 300 min, p = 0.001), less intraoperative blood loss (50 vs. 300 ml, p < 0.001), lower incidence of postoperative complications (32.0% vs. 15.0%, p = 0.005), shorter postoperative hospital stay (8 vs. 14 days, p < 0.001), and excision of more lateral pelvic lymph nodes (9 vs. 7, p = 0.025) than those in the open LPND group. The 3-year overall survival (p = 0.581) and 3-year disease-free survival (p = 0.745) rates were similar between the groups, and LPNM was an independent predictor of survival.

Conclusion: Laparoscopic LPND is technically safe and feasible with favourable short-term results and similar oncological outcomes as open surgery in selected patients.
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http://dx.doi.org/10.1111/codi.16223DOI Listing
June 2022

Theoretical modeling of ice lithography on amorphous solid water.

Nanoscale 2022 Jun 30;14(25):9045-9052. Epub 2022 Jun 30.

Key Laboratory of 3D Micro/Nano Fabrication and Characterization of Zhejiang Province, School of Engineering, Westlake University, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China.

Due to the perfection of the nanofabrication in nanotechnology and nanoscience, ice lithography (IL) by patterning ice thin-films with a focused electron beam, as a significant derivative technology of electron beam lithography (EBL), is attracting growing attention, evoked by its advantages over traditional EBL with respects of -fabrication, high efficiency, high accuracy, limited proximity effect, three-dimensional (3D) profiling capability, . However, theoretical modeling of ice lithography for replicated profiles on the ice resist (amorphous solid water, ASW) has rarely been reported so far. As the result, the development of ice lithography still stays at the experimental stage. The shortage of modeling methods limits our insight into the ice lithography capability, as well as theoretical anticipations for future developments of this emerging technique. In this work, an e-beam induced etching ice model based on the Monte Carlo algorithm for point/line spread functions is established to calculate the replicated profiles of the resist by ice lithography. To testify the fidelity of the modeling method, systematic simulations of the ice lithography property under the processing parameters of the resist thickness, electron accelerating voltage and actual patterns are performed. Theoretical comparisons between the IL on ASW and the conventional EBL on polymethyl methacrylate (PMMA) show superior properties of IL over EBL in terms of the minimum feature size, the highest aspect ratio, 3D nanostructure/devices, . The success in developing a modeling method for ice lithography, as reported in this paper, offers a powerful tool in characterizing ice lithography up to the theoretical level and down to molecular scales.
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http://dx.doi.org/10.1039/d2nr00594hDOI Listing
June 2022

Error analysis in calculation and interpretation of AFM tip-surface interaction forces.

Adv Colloid Interface Sci 2022 Aug 2;306:102710. Epub 2022 Jun 2.

Chongqing Key Laboratory of Soil Multi-Scale Interfacial Processes, College of Resources and Environment, Southwest University, Chongqing 400715, PR China. Electronic address:

This review addresses some possible errors in calculation and interpretation of AFM tip-surface interaction forces. These usually ignored errors can affect the accuracy and correctness of the interpretation results obtained from measured interaction forces, thus hindering the application of AFM technology in related fields of colloid and interface science. Based on comprehensive analysis and assessment, three important aspects in the existing literature that may introduce significant errors in calculation and interpretation of AFM tip-surface interaction forces have been identified, and corresponding reasonable suggestions have been proposed. (1) The frequently used over-approximated electrostatic force formulas can cause great errors in the electrostatic force and the fitting of surface potential and surface charge density. Therefore, adequate electrostatic force calculation methods, like linear superposition approximation (LSA) or exact numerical solutions, should be used. (2) The over-approximated AFM tip-surface interaction models (spherical tip and flat tip-flat surface interaction models (s-f and f-f)) will lead to large errors in the electrostatic force and van der Waals force, and the subsequently fitted surface potential, surface charge density, and Hamaker constant. Therefore, the conical tip with spherical end and the conical tip with flat circular end-flat surface interaction models (cs-f and cf-f) rather than the over-approximated models (s-f and f-f) should be applied. Besides, it is recommended to use cf-f instead of cs-f to measure the interaction forces for more accuracy. (3) The inaccurately obtained (usually by SEM image) AFM tip geometry parameters (radius and half angle) have significant impacts on the fitting results of surface potential, surface charge density, and Hamaker constant. More accurate AFM tip geometry parameters and reasonable assessment of errors in calculation and interpretation are necessary.
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http://dx.doi.org/10.1016/j.cis.2022.102710DOI Listing
August 2022

Genetic Dissection of Three Major Quantitative Trait Loci for Spike Compactness and Length in Bread Wheat ( L.).

Front Plant Sci 2022 23;13:882655. Epub 2022 May 23.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.

Spike compactness (SC) and length (SL) are the components of spike morphology and are strongly related to grain yield in wheat ( L.). To investigate quantitative trait loci (QTL) associated with SC and SL, a recombinant inbred lines (RIL) population derived from the cross of Bailangmai (BLM, a Tibet landrace) and Chuanyu 20 (CY20, an improved variety) was employed in six environments. Three genomic regions responsible for SC and SL traits were identified on chromosomes 2A and 2D using bulked segregant exome sequencing (BSE-Seq). By constructing genetic maps, six major QTL were repeatedly detected in more than four environments and the best linear unbiased estimation (BLUE) datasets, explaining 7.00-28.56% of the phenotypic variation and the logarithm of the odd (LOD) score varying from 2.50 to 13.22. They were co-located on three loci, designed as , , and , respectively. Based on the flanking markers, their interactions and effects on the corresponding trait and other agronomic traits were also analyzed. Comparison analysis showed that and were possibly two novel loci for SC and SL. and showed pleiotropic effects on plant height and grain morphology, while showed effects on spikelet number per spike (SNS) and grain width (GW). Based on the gene annotation, orthologous search, and spatiotemporal expression patterns of genes, and for , and and for were considered as potential candidate genes, respectively. These results will be useful for fine mapping and developing new varieties with high yield in the future.
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http://dx.doi.org/10.3389/fpls.2022.882655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168683PMC
May 2022

Correction: Study on the Action Mechanism of Dkk-1, TGF-β1 and TNF-α Expression Levels in Dupuytren's Contracture.

Handchir Mikrochir Plast Chir 2022 Apr 8;54(2):E1. Epub 2022 Jun 8.

The third Affiliated Hospital of Inner Mongolia Medicial University.

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http://dx.doi.org/10.1055/a-1860-8823DOI Listing
April 2022

Multiplicity and dynamics of social representations of the COVID-19 pandemic on Chinese social media from 2019 to 2020.

Inf Process Manag 2022 Jul 31;59(4):102990. Epub 2022 May 31.

Department of Communication, University of California Davis, Davis, CA, USA.

Documenting the emergent social representations of COVID-19 in public communication is necessary for critically reflecting on pandemic responses and providing guidance for global pandemic recovery policies and practices. This study documents the dynamics of changing social representations of the COVID-19 pandemic on one of the largest Chinese social media, Weibo, from December 2019 to April 2020. We draw on the social representation theory (SRT) and conceptualize topics and topic networks as a form of social representation. We analyzed a dataset of 40 million COVID-19 related posts from 9.7 million users (including the general public, opinion leaders, and organizations) using machine learning methods. We identified 12 topics and found an expansion in social representations of COVID-19 from a clinical and epidemiological perspective to a broader perspective that integrated personal illness experiences with economic and sociopolitical discourses. Discussions about COVID-19 science did not take a prominent position in the representations, suggesting a lack of effective science and risk communication. Further, we found the strongest association of social representations existed between the public and opinion leaders and the organizations' representations did not align much with the other two groups, suggesting a lack of organizations' influence in public representations of COVID-19 on social media in China.
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http://dx.doi.org/10.1016/j.ipm.2022.102990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9151658PMC
July 2022

Synthesis and Biochemical Evaluation of 8-Indeno[1,2-]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors.

Molecules 2022 May 23;27(10). Epub 2022 May 23.

School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China.

The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CL) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8-indeno[1,2-]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CL. Among them, the representative compound displayed inhibitory activity with an IC of 1.28 ± 0.17 μM against SARS-CoV-2 3CL. Molecular docking of against 3CL was performed and the binding mode was rationalized. These preliminary results provide a unique prototype for the development of novel inhibitors against SARS-CoV-2 3CL.
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http://dx.doi.org/10.3390/molecules27103359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145245PMC
May 2022

Risk factors of chylous ascites and its relationship with long-term prognosis in laparoscopic D3 lymphadenectomy for right colon cancer.

Langenbecks Arch Surg 2022 May 20. Epub 2022 May 20.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China.

Background: Chylous ascites (CA) after laparoscopic D3 lymphadenectomy for right colon cancer is not rare. However, the risk factors for CA have not been fully explored. Few studies have investigated the effect of CA on long-term prognosis.

Methods: The clinical data of patients with right colon cancer who underwent laparoscopic D3 lymphadenectomy in five centers from January 2013 to December 2018 were retrospectively collected. Univariate and multivariate analyses were performed to determine the clinicopathological factors associated with CA. Then, the long-term prognosis of patients with and without CA was compared by propensity score matching and Kaplan-Meier survival analysis.

Results: The incidence of CA was 4.4% (48/1090). Pathological T stage (p = 0.025), dissection along the left side of the superior mesenteric artery (p < 0.001) and the number of retrieved lymph nodes (p < 0.001) were independent risk factors for CA. After propensity score matching, 48 patients in the CA group and 353 patients in the non-CA group were enrolled. Kaplan-Meier survival analysis indicated that CA was not associated with overall survival (p = 0.454) and disease-free survival (p = 0.163). In patients with stage III right colon cancer, there were no significant differences in overall survival (p = 0.501) and disease-free survival (p = 0.254).

Conclusions: Pathological T stage, number of retrieved lymph nodes, and left side dissection along the superior mesenteric artery were independent risk factors for CA after laparoscopic D3 lymphadenectomy. CA does not impair the oncological outcomes of patients.
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http://dx.doi.org/10.1007/s00423-022-02527-3DOI Listing
May 2022

A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape.

Small Methods 2022 07 18;6(7):e2200387. Epub 2022 May 18.

State Key Laboratory of Respiratory Disease, Institute of Infectious Disease, Guangzhou 8th People's Hospital & The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel β-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of β-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant.
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http://dx.doi.org/10.1002/smtd.202200387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347709PMC
July 2022

Structured training curriculums for transanal total mesorectal excision in China: refinement is needed.

Ann Transl Med 2022 Apr;10(8):489

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Transanal total mesorectal excision (TaTME) is an alternative for mid-low rectal cancer. In China, this procedure has been performed in high-volume centers with structured training curriculums. The efficacy of the TaTME structured training curriculums in China is still unclear. This multicenter study aimed to explore the effectiveness of the structured training curriculums in China.

Methods: Seven high-volume centers in China participated in this study. The first 25 patients who underwent TaTME in each center were enrolled. In the cohort, patients were divided into 3 groups. The first 5 procedures (group 1) were performed under proctoring according to the requirement of structured training curriculums. The latter 20 cases without proctoring were split into 2 groups (10 cases in each group, groups 2 and 3) according to the order of operation date. The baseline characteristics, perioperative complications, and pathological outcomes were compared between groups 1 and 2, as well as between groups 2 and 3.

Results: Symptomatic anastomotic leakage (AL) occurred in 18.6% of the patients in group 2 compared with 5.7% in group 1 (P=0.08) and 5.0% in group 3 (P=0.04). Seven (11.3%) patients in group 2 developed defecation disorders whereas no patients had this complication in group 3 (P=0.02). Compared with group 2, the operative time was shorter (235 223 min, P=0.40), while the rates of intraoperative complications (15.7% 5.7%, P=0.10), postoperative complications (31.3% 25.7%, P=0.06), AL (20.0% 8.6%, P=0.04), and positive distal resection margin (DRM) (7.5% 2.9%, P=0.27) were lower in group 3.

Conclusions: The effect of the structured training curriculums was acceptable but needed further improvement. The prevalence of anastomosis-related complications and the quality control of specimens are still not optimal, and measures for refinement (for example, more cases under proctoring) are needed in the curriculums.
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http://dx.doi.org/10.21037/atm-22-1693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096368PMC
April 2022

Transporters in Drug Development: International Transporter Consortium Update on Emerging Transporters of Clinical Importance.

Clin Pharmacol Ther 2022 May 13. Epub 2022 May 13.

Department of Pharmaceutical Sciences, University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, Ontario, Canada.

During its fourth transporter workshop in 2021, the International Transporter Consortium (ITC) provided updates on emerging clinically relevant transporters for drug development. Previously highlighted and new transporters were considered based on up-to-date clinical evidence of their importance in drug-drug interactions and potential for altered drug efficacy and safety, including drug-nutrient interactions leading to nutrient deficiencies. For the first time, folate transport pathways (PCFT, RFC, and FRα) were examined in-depth as a potential mechanism of drug-induced folate deficiency and related toxicities (e.g., neural tube defects and megaloblastic anemia). However, routine toxicology studies conducted in support of drug development appear sufficient to flag such folate deficiency toxicities, whereas prospective prediction from in vitro folate metabolism and transport inhibition is not well enough established to inform drug development. Previous suggestion of a retrospective study of intestinal OATP2B1 inhibition to explain unexpected decreases in drug exposure were updated. Furthermore, when the absorption of a new molecular entity is more rapid and extensive than can be explained by passive permeability, evaluation of the OATP2B1 transport may be considered. Emerging research on hepatic and renal OAT2 is summarized, but current understanding of the importance of OAT2 was deemed insufficient to justify specific consideration for drug development. Hepatic, renal, and intestinal MRPs (MRP2, MRP3, and MRP4) were revisited. MRPs may be considered when they are suspected to be the major determinant of drug disposition (e.g., direct glucuronide conjugates); MRP2 inhibition as a mechanistic explanation for drug-induced hyperbilirubinemia remains justified. There were no major changes in recommendations from previous ITC whitepapers.
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http://dx.doi.org/10.1002/cpt.2644DOI Listing
May 2022

Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Nat Med 2022 05 12;28(5):974-981. Epub 2022 May 12.

Shanghai Pudong New Area People's Hospital, Shanghai, China.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was -1.02% (-1.11, -0.93) in the dorzagliatin group and -0.36% (-0.45, -0.26) in the placebo group (estimated treatment difference, -0.66%; 95% CI: -0.79, -0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile ( NCT03141073 ).
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http://dx.doi.org/10.1038/s41591-022-01803-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117147PMC
May 2022

Follistatin-like 1 (FSTL1) interacts with Wnt ligands and Frizzled receptors to enhance Wnt/β-catenin signaling in obstructed kidneys in vivo.

J Biol Chem 2022 07 4;298(7):102010. Epub 2022 May 4.

Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China; Guangdong-Hong Kong Joint Laboratory for Immune and Genetic Kidney Disease, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, and The Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Follistatin (FS)-like 1 (FSTL1) is a member of the FS-SPARC (secreted protein, acidic and rich in cysteine) family of secreted and extracellular matrix proteins. The functions of FSTL1 have been studied in heart and lung injury as well as in wound healing; however, the role of FSTL1 in the kidney is largely unknown. Here, we show using single-cell RNA-Seq that Fstl1 was enriched in stromal cells in obstructed mouse kidneys. In addition, immunofluorescence demonstrated that FSTL1 expression was induced in fibroblasts during kidney fibrogenesis in mice and human patients. We demonstrate that FSTL1 overexpression increased renal fibrosis and activated the Wnt/β-catenin signaling pathway, known to promote kidney fibrosis, but not the transforming growth factor β (TGF-β), Notch, Hedgehog, or Yes-associated protein (YAP) signaling pathways in obstructed mouse kidneys, whereas inhibition of FSTL1 lowered Wnt/β-catenin signaling. Importantly, we show that FSTL1 interacted with Wnt ligands and the Frizzled (FZD) receptors but not the coreceptor lipoprotein receptor-related protein 6 (LRP6). Specifically, we found FSTL1 interacted with Wnt3a through its extracellular calcium-binding (EC) domain and von Willebrand factor type C-like (VWC) domain, and with FZD4 through its EC domain. Furthermore, we show that FSTL1 increased the association of Wnt3a with FZD4 and promoted Wnt/β-catenin signaling and fibrogenesis. The EC domain interacting with both Wnt3a and FZD4 also enhanced Wnt3a signaling. Therefore, we conclude that FSTL1 is a novel extracellular enhancer of the Wnt/β-catenin pathway.
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http://dx.doi.org/10.1016/j.jbc.2022.102010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234244PMC
July 2022

Spectral filter in short-wave infrareds based on a metasurface on silicon-on-insulator with polarizing bandpass.

Appl Opt 2022 Apr;61(10):2490-2496

Spectral filters with polarimetric character in short-wave infrareds are urgently needed because of their broad applications in optic-fiber communications, polarimetric detections, and imaging. Based on our earlier progress in developing polarimetric devices in infrared wavelengths, in this work, a plasmonic-metasurface-based polarization-dependency multi-channel narrowband filter in short-wave infrareds was developed. To meet the requirement by the developing trend of polarimetric detection/spectral imaging in short-wave infrareds, a resonant cavity in the form of the Au hat/elliptical / pillars/Au layer as the filters was proposed. Numerical simulations by finite-difference time-domain (FDTD) show resonant and polarized transmissions of the designed devices to infrared light in short wavelengths, and the peak positions are relevant to the structural dimensions. Optical characteristics of the filters, fabricated by electron beam lithography/dry-etch technique, agree well with the simulated behavior. To enhance the transmission efficiency to the applicable level, nanoprocessing of the filters still needs to be optimized. Nevertheless, the progress reported is promising for this new type of spectral filters based on modern metasurfaces.
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http://dx.doi.org/10.1364/AO.453891DOI Listing
April 2022

Mechanisms of the Jian Pi Tiao Gan Yin in the treatment of simple obesity revealed by network pharmacology.

Ann Transl Med 2022 Mar;10(6):335

Department of Geriatrics, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.

Background: This study sought to examine the mechanism of the Jian Pi Tiao Gan Yin in the treatment of obesity by network pharmacology.

Methods: The active components and corresponding targets of the Jian Pi Tiao Gan Yin were identified using the traditional Chinese medicine systems pharmacology database and analysis platform, and the obesity-related targets were acquired from the Online Mendelian Inheritance in Man database. The drug and disease targets were also identified. Cytoscape software was used to construct the "active component target" network diagram. The protein-protein interaction network was drawn using the Search Tool for the Retrieval of Interacting Genes/Proteins platform, and the Cytoscape MCODE plugin was used to find clusters for the protein cluster analysis. The gene annotation and analysis were performed with the Metascape database via functional databases, such as the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and Autodock and PyMOL were used for the molecular docking.

Results: The GO analysis identified 244 target genes of the Jian Pi Tiao Gan Yin, 1,378 targets of obesity, and 123 targets of drug and disease. Additionally, 208 biological process items, 38 molecular function items, and 33 cell component items were also identified. The KEGG pathway analysis identified the hypoxia-inducible factor, forkhead box O, cyclic adenosine monophosphate, and vascular endothelial growth factor signaling pathways. The results of the molecular docking showed that the main active components of the Jian Pi Tiao Gan Yin in the treatment of obesity were quercetin, kaempferol, stigmasterol, luteolin, isorhamnetin, β-sitosterol, sapogenin, tanshinone, and formononetin, all of which have been proven to bind to core obesity-related proteins, such as AKT1, interleukin-6 (), vascular endothelial growth factor A (), tumor necrosis factor (), tumor protein 53 (), prostaglandin-endoperoxide synthase 2 (), caspase-3 (), mitogen-activated protein kinase 1 (), JUN, and epidermal growth factor (). Thus, our study revealed the potential mechanism of the Jian Pi Tiao Gan Yin as a multi-component, multi-target, and multi-channel treatment for obesity. These findings lay the foundation for further studies on the mechanism of the Jian Pi Tiao Gan Yin in obesity treatment.

Conclusions: The Jian Pi Tiao Gan Yin can be used as a multi-component, multi-target, and multi-channel treatment for obesity.
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http://dx.doi.org/10.21037/atm-22-553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011268PMC
March 2022

Jian Pi Tiao Gan Yin alleviates obesity phenotypes through mTORC1/SREBP1 signaling and .

Ann Transl Med 2022 Mar;10(6):291

Department of Geriatrics, the First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.

Background: Obesity has been considered as a leading cause of multiple metabolic syndromes, such as type 2 diabetes and hypertension cardiovascular diseases. Jian Pi Tiao Gan Yin (JPTGY), a Chinese herb preparation, is used to treat obesity of liver qi stagnation and spleen deficiency. The mechanism of action of JPTGY in obesity remains unclear. This study evaluated the effect of JPTGY on obesity.

Methods: The mechanism of action of JPTGY on obesity was investigated in high-fat diet (HFD)-induced obese mice and palmitic acid-treated 3T3-L1 cells. Lipid droplet accumulation was detected using oil red O staining. Factors associated with lipid accumulation were detected by western blotting.

Results: Treatment with JPTGY reduced HFD-induced adiposity and body weight gain. JPTGY increased the levels of brown adipose tissue biomarkers in obese mice and palmitic acid-treated 3T3-L1 cells, including peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α) and uncoupling protein-1 (UCP-1). Meanwhile, the protein expression of white adipose tissue biomarkers, such as AGT, primary subtalar arthrodesis (PSTA), and endothelin receptor type A (EDNRA), was decreased in obese mice and palmitic acid-treated 3T3-L1 cells. JPTGY affects browning of 3T3-L1 cells through mechanistic target of rapamycin complex 1 (mTORC1) signaling. JPTGY decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), sterol regulatory element binding protein (SREBP), and FAS. Treatment with the mTOR activator MHY reversed JPTGY-mediated protein expression.

Conclusions: We concluded that JPTGY relieved obesity phenotypes through mTORC1/SREBP1 signaling and . JPTGY may benefit the attenuation of obesity.
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http://dx.doi.org/10.21037/atm-22-685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011225PMC
March 2022

Study on the Action Mechanism of Dkk-1, TGF-β1 and TNF-α Expression Levels in Dupuytren's Contracture.

Handchir Mikrochir Plast Chir 2022 Apr 13;54(2):149-154. Epub 2022 Apr 13.

The third Affiliated Hospital of Inner Mongolia Medicial University.

Background: The biological mechanism of Dupuytren's contracture needs to be further studied in order to minimize postoperative recurrence and provide a pathological basis for the development of new therapeutic targets.

Methods: HE staining, immunohistochemistry, PCR and western blotting were performed in pathological palmar aponeurosis specimens and normal palmar aponeurosis tissues for comparative study.

Results: (1) TNF-α expression was up-regulated: TNF-α mRNA was more highly expressed in the pathological tissues of DD patients than in the CT group, P < 0.05, and the difference between the two groups was statistically significant; (2) Dkk-1 expression was down-regulated: Dkk-1 mRNA was lower expressed in the pathological tissues of DD patients than in the CT group, P < 0.05, and the difference between the two groups was statistically significant; (3) TGF-β1 expression was up-regulated: TGF-β1 mRNA was higher expressed in the pathological tissues of DD patients than in the CT group, P < 0.05, and the difference between the two groups was statistically significant; (4) Pearson correlation analysis suggested that TNF-α expression was positively correlated with TGF-β1 expression, TNF-α expression was negatively correlated with DKK-1 expression, and TGF-β1 expression was negatively correlated with DKK-1 expression.

Conclusion: TNF-α, DKK-1 and TGF-β1 may play a role in the pathogenesis of palmar aponeurosis contracture, and there is a relationship between them. The study of the relationship between the three and their related signaling pathways provides a therapeutic target and a basis for the prevention and early treatment of palmar aponeurotic contracture.
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http://dx.doi.org/10.1055/a-1794-5668DOI Listing
April 2022

Unbound Brain-to-Plasma Partition Coefficient, K-a Game Changing Parameter for CNS Drug Discovery and Development.

Pharm Res 2022 Jul 11;39(7):1321-1341. Epub 2022 Apr 11.

Department of Pharmacy, Uppsala University, Box 580, Uppsala, Sweden.

Purpose: More than 15 years have passed since the first description of the unbound brain-to-plasma partition coefficient (K) by Prof. Margareta Hammarlund-Udenaes, which was enabled by advancements in experimental methodologies including cerebral microdialysis. Since then, growing knowledge and data continue to support the notion that the unbound (free) concentration of a drug at the site of action, such as the brain, is the driving force for pharmacological responses. Towards this end, K is the key parameter to obtain unbound brain concentrations from unbound plasma concentrations.

Methods: To understand the importance and impact of the K concept in contemporary drug discovery and development, a survey has been conducted amongst major pharmaceutical companies based in Europe and the USA. Here, we present the results from this survey which consisted of 47 questions addressing: 1) Background information of the companies, 2) Implementation, 3) Application areas, 4) Methodology, 5) Impact and 6) Future perspectives.

Results And Conclusions: From the responses, it is clear that the majority of the companies (93%) has established a common understanding across disciplines of the concept and utility of K as compared to other parameters related to brain exposure. Adoption of the K concept has been mainly driven by individual scientists advocating its application in the various companies rather than by a top-down approach. Remarkably, 79% of all responders describe the portfolio impact of K implementation in their companies as 'game-changing'. Although most companies (74%) consider the current toolbox for K assessment and its validation satisfactory for drug discovery and early development, areas of improvement and future research to better understand human brain pharmacokinetics/pharmacodynamics translation have been identified.
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http://dx.doi.org/10.1007/s11095-022-03246-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246790PMC
July 2022
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