Publications by authors named "Hui Zheng"

1,236 Publications

  • Page 1 of 1

Acupuncture for Patients With Chronic Tension-Type Headache: A Randomized Controlled Trial.

Neurology 2022 Jun 22. Epub 2022 Jun 22.

The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China

Background And Objectives: Whether acupuncture is effective for chronic tension-type headache (CTTH) is inconclusive. We aimed to examine the effectiveness of acupuncture with a follow-up period of 32 weeks.

Methods: We conducted a randomized controlled trial, and 218 participants who were diagnosed with CTTH were recruited from June 2017 to September 2020. The participants in the intervention group received 20 sessions of true acupuncture (TA group) over 8 weeks. The acupuncture treatments were standardized across participants, and each acupuncture site was needled to achieve sensation. Each treatment session lasted 30 minutes. The participants in the control group received the same sessions and treatment frequency of superficial acupuncture (SA group)-defined as a type of sham control by avoiding sensation at each acupuncture site. The main outcome was the responder rate at 16 weeks after randomization (week 16) and was followed up at week 32. A responder was defined as a participant who reported at least a 50% reduction in the monthly number of headache days (MHDs).

Results: Our study included 218 participants (mean age: 43.1 years, mean disease duration: 130 months, MHDs: 21.5 days). The responder rate was 68.2% in the TA group (n=110) versus 48.1% in the SA group (n=108) at week 16 (odds ratio, 2.65; 95%CI, 1.5 to 4.77; p<0.001); and it was 68.2% in the TA group versus 50% in the SA group at week 32 (odds ratio, 2.4; 95%CI, 1.36 to 4.3; p<0.001). The reduction in MHDs was 13.1±9.8 days in the TA group versus 8.8±9.6 days in the SA group at week 16 (mean difference, 4.3 days; 95%CI, 2.0 to 6.5; p<0.001), and the reduction was 14±10.5 days in the TA group versus 9.5±9.3 days in the SA group at week 32 (mean difference, 4.5 days; 95%CI, 2.1 to 6.8; p<0.001). Four mild adverse events were reported; three in the TA group versus one in the SA group.

Conclusion: The 8-week TA treatment was effective for the prophylaxis of CTTH. Further studies might focus on the cost-effectiveness of the treatment.

Trial: Registration : ClinicalTrials.gov: NCT03133884 (https://clinicaltrials.gov/ct2/show/NCT03133884) CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that acupuncture (achieving deqi sensation) reduces mean headache days (per month) in patients with chronic tension-type headache.
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http://dx.doi.org/10.1212/WNL.0000000000200670DOI Listing
June 2022

One-Pot Synthesis of Hexamethylenetetramine Coupled with H Evolution from Methanol and Ammonia by a Pt/TiO Nanophotocatalyst.

ACS Omega 2022 Jun 6;7(23):19614-19621. Epub 2022 Jun 6.

State Key Laboratory of Physical Chemistry of Solid Surfaces, National Engineering Laboratory for Green Chemical Productions of Alcohols-Ethers-Esters, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Utilization of solar energy for photocatalytic H evolution coupled with value-added chemical synthesis is a promising avenue to address energy and environmental crises. Here, we report the hexamethylenetetramine (HMT) synthesis and H evolution from methanol and ammonia in one pot using a nanophotocatalyst of the conventional semiconductor TiO (P25) loaded with Pt (Pt/P25). The addition of ammonia inhibits byproduct ethylene glycol formation, promotes H evolution, and obtains HMT with high selectivity (>99.0%). The Pt valence state is regulated by calcination and reduction treatment, indicating that Pt/P25 is a stable catalyst for the photocatalytic synthesis of HMT from methanol and ammonia. The optimized formation rates of H and HMT are 71.53 and 11.39 mmol g h, respectively. This work provides a green and sustainable pathway for the photocatalytic HMT synthesis coupled with H evolution under mild conditions.
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http://dx.doi.org/10.1021/acsomega.2c01323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202295PMC
June 2022

Passively scanned, single-fiber optical coherence tomography probes for gastrointestinal devices.

Lasers Surg Med 2022 Jun 16. Epub 2022 Jun 16.

Harvard Medical School, Boston, Massachusetts, USA.

Background/objectives: Optical coherence tomography (OCT) uses low coherence interferometry to obtain depth-resolved tissue reflectivity profiles (M-mode) and transverse beam scanning to create images of two-dimensional tissue morphology (B-mode). Endoscopic OCT imaging probes typically employ proximal or distal mechanical beam scanning mechanisms that increase cost, complexity, and size. Here, we demonstrate in the gastrointestinal (GI) tracts of unsedated human patients, that a passive, single-fiber probe can be used to guide device placement, conduct device-tissue physical contact sensing, and obtain two-dimensional OCT images via M-to-B-mode conversion.

Materials And Methods: We designed and developed ultrasmall, manually scannable, side- and forward-viewing single fiber-optic probes that can capture M-mode OCT data. Side-viewing M-mode OCT probes were incorporated into brush biopsy devices designed to harvest the microbiome and forward-viewing M-mode OCT probes were integrated into devices that measure intestinal potential difference (IPD). The M-mode OCT probe-coupled devices were utilized in the GI tract in six unsedated patients in vivo. M-mode data were converted into B-mode images using an M-to-B-mode conversion algorithm. The effectiveness of physical contact sensing by the M-mode OCT probes was assessed by comparing the variances of the IPD values when the probe was in physical contact with the tissue versus when it was not. The capacity of forward- and side-viewing M-mode OCT probes to produce high-quality B-mode images was compared by computing the percentages of the M-to-B-mode images that showed close contact between the probe and the luminal surface. Passively scanned M-to-B-mode images were qualitatively compared to B-mode images obtained by mechanical scanning OCT tethered capsule endomicroscopy (TCE) imaging devices.

Results: The incorporation of M-mode OCT probes in these nonendoscopic GI devices safely and effectively enabled M-mode OCT imaging, facilitating real-time device placement guidance and contact sensing in vivo. Results showed that M-mode OCT contact sensing improved the variance of IPD measurements threefold and side-viewing probes increased M-to-B-mode image visibility by 10%. Images of the esophagus, stomach, and duodenum generated by the passively scanned probes and M-to-B-mode conversion were qualitatively superior to B-mode images obtained by mechanically scanning OCT TCE devices.

Conclusion: These results show that passive, single optical fiber OCT probes can be effectively utilized for nonendoscopic device placement guidance, device contact sensing, and two-dimensional morphologic imaging in the human GI tract in vivo. Due to their small size, lower cost, and reduced complexity, these M-mode OCT probes may provide an easier avenue for the incorporation of OCT functionality into endoscopic/nonendoscopic devices.
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http://dx.doi.org/10.1002/lsm.23576DOI Listing
June 2022

Evidence for Dopamine Abnormalities Following Acute Methamphetamine Exposure Assessed by Neuromelanin-Sensitive Magnetic Resonance Imaging.

Front Aging Neurosci 2022 30;14:865825. Epub 2022 May 30.

Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, China.

Background: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is a newly developed MRI technique that provides a non-invasive way to indirectly measure of dopamine (DA) function. This study aimed to determine NM concentrations in brain regions following acute methamphetamine (MA) administration using NM-MRI and to explore whether NM-MRI can be used as a biomarker of DA function in non-neurodegenerative diseases.

Methods: Baseline NM-MRI, T1-weighted and T2-weighted images were acquired from 27 rats before drug/placebo injection. The control group ( = 11) received acute placebo (Normal saline), while the experimental group ( = 16) received acute MA. NM-MRI scans were performed 5, 30, 60 and 90 min after injection. Regions of interest (ROIs), including the caudate putamen (CP), nucleus accumbens (NAc), hippocampus (HIP), substantia nigra (SN) and crus cerebri (CC), were manually drawn by an experienced radiologist. NM-MRI signal intensity in five brain regions at different time points (baseline and 5, 30, 60, and 90 min) were analyzed.

Results: In both the control and experimental groups, at each time point (baseline and 5, 30, 60, and 90 min), the SN exhibited significantly higher NM-MRI signal intensity than the other brain regions ( < 0.05). In addition, acute MA administration resulted in a continuous upward trend in NM-MRI signal intensity in each brain region over time. However, there was no such trend over time in the control group. The NM-MRI signal intensity of SN in the experimental group was significantly higher at the 60 and 90 min compared with that in the control group ( values were 0.042 and 0.042 respectively). Within experimental group, the NM-MRI signal intensity of SN was significantly higher at the 60 and 90 min compared with that before MA administration ( values were 0.023 and 0.011 respectively). Increased amplitudes and rates of NM-MRI signal intensity were higher in the SN than in other brain regions after MA administration.

Conclusion: Our results indicated that NM was mainly deposited in the SN, and the conversion of DA to NM was most significant in the SN after acute MA exposure. Increased DA release induced by acute MA exposure may lead to increased accumulation of NM in multiple brain regions that can be revealed by NM-MRI. NM-MRI may serve as a powerful imaging tool that could have diverse research and clinical applications for detecting pathological changes in drug addiction and related non-neurodegenerative diseases.
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http://dx.doi.org/10.3389/fnagi.2022.865825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190254PMC
May 2022

Synergistic effect of discrete ultrasonic and HO on physicochemical properties of chitosan.

Carbohydr Polym 2022 Sep 10;291:119598. Epub 2022 May 10.

College of Food Science, Shenyang Agricultural University, Shenyang 110866, China. Electronic address:

Synergistic degradation of chitosan by discrete ultrasonic and HO was investigated. The effects of ultrasonic time, ultrasonic power, chitosan concentration, and HO concentration were evaluated. The results revealed that ultrasonic power, HO concentration and ultrasonic time were positively correlated with degradation rate, while chitosan concentration was negative. The results of degradation kinetics revealed that the synergistic degradation process was consistent with the first-order reaction. Changes of characterization of chitosan were analyzed by FTIR, C NMR, XRD, SEM, and AFM analysis. The results indicated that the synergistic degradation did not destroy the pyranose ring. The crystal structure of degraded chitosan was destroyed, and the molecular conformation changed significantly. The antioxidant activity of the original and degraded chitosan was determined by DPPH and reducing power assays. The degraded chitosan had higher antioxidant activity. All results showed that the synergistic degradation of discrete ultrasound and HO was a feasible method for large-scale low molecular weight chitosan production.
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http://dx.doi.org/10.1016/j.carbpol.2022.119598DOI Listing
September 2022

Identification of a novel Calpain-2-SRC feed-back loop as necessity for β-Catenin accumulation and signaling activation in hepatocellular carcinoma.

Oncogene 2022 Jun 13. Epub 2022 Jun 13.

Department of clinical laboratory, Shanghai Cancer center, Fudan University, Shanghai, 200032, China.

Rapid progression is the major cause of the poor prognosis of hepatocellular carcinoma (HCC); however, the underlying mechanism remained unclear. Here, we found Calpain-2 (CAPN2), a well-established protease that accelerates tumor progression in several malignancies, is overexpressed in HCC and acts as an independent predictor for poor outcomes. Furthermore, CAPN2 promoted the proliferation and invasion of HCC, and showed a positive correlation with the levels of invasion-related markers. Mechanistically, a novel CAPN2-SRC positive regulatory loop was identified upstream of β-catenin to prevent its ubiquitination and degradation, and subsequently promoted HCC progression: CAPN2 could proteolyze PTP1B to form a truncation of approximately 42 kDa with increased phosphatase activity, resulting in reduced SRC Y530 phosphorylation and increased SRC kinase activity; meanwhile, CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation. Interestingly, the CAPN2-SRC loop could not only restrain most of cytoplasmic β-catenin degradation by inhibiting GSK3β pathway, but also prevented TRIM33-induced nuclear β-catenin degradation even in β-catenin-mutant cells. Present study identified a CAPN2-SRC positive loop responsible for intracellular β-catenin accumulation and signaling activation, and targeting CAPN2 protease activity might be a promising approach for preventing HCC progression.
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http://dx.doi.org/10.1038/s41388-022-02367-xDOI Listing
June 2022

MoS/WSe vdW Heterostructures Decorated with PbS Quantum Dots for the Development of High-Performance Photovoltaic and Broadband Photodiodes.

ACS Nano 2022 Jun 10. Epub 2022 Jun 10.

Lab for Nanoelectronics and NanoDevices, Department of Electronics Science and Technology, Hangzhou Dianzi University, Hangzhou 310018, China.

van der Waals heterostructures (vdWHs) overcoming the lattice and processing limitations of conventional heterostructures provide an opportunity to develop high-performance 2D vdWH solar cells and photodiodes. However, it is challenging to improve the sensitivity and response speed of 2D vdWH photovoltaic devices due to the low light absorption efficiency and electron/hole traps in heterointerfaces. Here, we design a PbS/MoS/WSe heterostructure photodiode in which a light-sensitive PbS quantum dot (QD) layer combined with a MoS/WSe heterostructure significantly enhances the photovoltaic response. The electron current in the heterostructure is increased by the effective collection of photogenerated electrons induced by PbS QDs. The device exhibits a broadband photovoltaic response from 405 to 1064 nm with a maximum responsivity of 0.76 A/W and a specific detectivity of 5.15 × 10 Jones. In particular, the response speed is not limited by multiple electron traps in the PbS QDs/2D material heterointerface, and a fast rising/decaying time of 43/48 μs and a -3 dB cutoff frequency of over 10 kHz are achieved. The negative differential capacitance and frequency dependence of capacitance demonstrate the presence of interface states in the MoS/WSe heterointerface that hamper the improvement of the response speed. The scheme to enhance photovoltaic performance without sacrificing response speed provides opportunities for the development of high-performance 2D vdWH optoelectronic devices.
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http://dx.doi.org/10.1021/acsnano.2c02012DOI Listing
June 2022

Mitochondrial Diabetes is Associated with tRNA A3243G and T14502C Mutations.

Diabetes Metab Syndr Obes 2022 3;15:1687-1701. Epub 2022 Jun 3.

Central Laboratory, Hangzhou First People's Hospital, Hangzhou, 310006, Zhejiang, People's Republic of China.

Background: Mutations in mitochondrial DNA (mtDNA) are associated with type 2 diabetes mellitus (T2DM). In particular, m.A3243G is the most common T2DM-related mtDNA mutation in many families worldwide. However, the clinical features and pathophysiology of m.A3243G-induced T2DM are largely undefined.

Methods: Two pedigrees with maternally inherited T2DM were underwent clinical, molecular and biochemical assessments. The mtDNA genes were PCR amplified and sequenced. Mitochondrial adenosine triphosphate (ATP) and reactive oxygen species (ROS) were measured in polymononuclear leukocytes derived from three patients with both the m.A3243G and m.T14502C mutations, three patients with only the m.A3243G mutation and three controls without these mutations. Moreover, and mutations were screened by PCR-Sanger sequencing.

Results: Members of the two pedigrees manifestated variable clinical phenotypes including diabetes and hearing and vision impairments. The age at onset of T2DM varied from 31 to 66 years, with an average of 41 years. Mutational analysis of mitochondrial genomes indicated the presence of the m.A3243G mutation in both pedigrees. Matrilineal relatives in one of the pedigrees harbored the coexisting of m.A3243G and m.T14502C mutations. Remarkably, the m.T14502C mutation, which causes the substitution of a conserved isoleucine for valine at position 58 in mRNA, may affect the mitochondrial respiratory chain functions. Biochemical analysis revealed that cell lines bearing both the m.A3243G and m.T14502C mutations exhibited greater reductions in ATP levels and increased ROS production compared with those carrying only the m.A3243G mutation. However, we did not find any mutations in the and genes.

Conclusion: Our study indicated that mitochondrial diabetes is associated with the tRNA A3243G and T14502C mutations.
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http://dx.doi.org/10.2147/DMSO.S363978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172734PMC
June 2022

Network Analysis of Eating Disorders Symptoms Co-occurring With Impulsive Personality Traits and Negative Mood States in Patients With Bulimia Nervosa.

Front Psychiatry 2022 18;13:899757. Epub 2022 May 18.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Bulimia nervosa (BN) is characterized by recurrent episodes of eating large amounts of food without control. Studies have found positive correlations of BN symptoms with impulsive traits and negative affect. However, the network relationship supporting BN symptoms is unclear.

Methods: The study participants included female BN patients (146) and healthy controls (HCs, 146). The participants were matched for age. All participants completed the Eating Disorder Examination Questionnaire 6.0, Barratt Impulsiveness Scale-11, Beck Anxiety Inventory, and Beck Depression Inventory. We characterized the centrality parameters of BN, impulsiveness, and anxiety and depression symptoms of BN patients compared with HCs.

Results: Among all symptoms in the constructed BN group network, Shape dissatisfaction had the highest strength. In the BN group network, three clusters of symptoms ("ED-specific symptoms," "impulsivity," and "anxiety and depression") were linked to each other by several symptoms. Compared to the HC network, impulsiveness was strongly associated with Concerns about Others Seeing One Eat in the BN network.

Conclusion: This study shows that ED-specific symptoms, i.e., Shape dissatisfaction, play a key role in BN. The cognition of "shape dissatisfaction" is a basis, and impulsivity and emotional symptoms are maintaining factors that may lead to BN development.
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http://dx.doi.org/10.3389/fpsyt.2022.899757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157589PMC
May 2022

The unbalanced behavioral activation and inhibition system sensitivity in internet gaming disorder: Evidence from resting-state Granger causal connectivity analysis.

Prog Neuropsychopharmacol Biol Psychiatry 2022 Jun 2;119:110582. Epub 2022 Jun 2.

Center for Cognition and Brain Disorders, the Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province, PR China; Institute of Psychological Science, Hangzhou Normal University, Hangzhou, Zhejiang Province, PR China. Electronic address:

Background: Patients with behavioral or substance addiction show an unbalanced behavioral activation system (BAS) and behavioral inhibition system (BIS) sensitivity. However, the relationship between internet gaming disorder (IGD) and BAS/BIS is obscure and the neurobiological mechanism underlying this relationship remains unclear.

Methods: We recruited 154 IGDs and 229 recreational game users (RGUs) in the current study. First, we explored the relationship between BAS/BIS and IGD. Second, subjects were subdivided into subgroups by BAS/BIS sensitivity. Third, whole-brain Granger causal connectivity (GCC) of striatum and amygdala subdivisions was estimated for the subgroup. Fourth, mediation analysis was performed to explore the role of connectivity in the relationship between IGD and BAS/BIS sensitivity.

Results: We found the IGD group scored higher than the RGU on BIS and BASf (fun-seeking) sensitivity. Then, we identified 4 (2*2) subgroups: low/high risk of IGD with low/high BAS/BIS sensitivity groups. Two-way ANCOVA main results of interaction effects showed that in the high BAS/BIS group, the RGU exhibited increased strength in the GCC from the left putamen to the right cuneus, and the IGD exhibited decreased strength in the GCC from the right medial frontal gyrus to the caudate, from the left superior frontal gyrus to the centromedial amygdala, and from the right superior parietal lobule to the left laterobasal amygdala. Moreover, the GCC from the centromedial amygdala to the middle frontal gyrus mediated the directional relationship between BIS and IAT (Young's internet addiction test) scores.

Conclusions: The IGD individuals exhibited higher BIS and BAS-fun seeking sensitivity. Moreover, IGD with unbalanced BAS/BIS sensitivity exhibited alternative connectivity patterns involving amygdala and striatum subdivisions. These findings suggest a neurobiological mechanism for an alternation between IGD and RGU with different BAS/BIS sensitivity.
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http://dx.doi.org/10.1016/j.pnpbp.2022.110582DOI Listing
June 2022

Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors.

Nat Cancer 2022 May 30. Epub 2022 May 30.

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Evasion of antitumor immunity and resistance to therapies in solid tumors are aided by an immunosuppressive tumor microenvironment (TME). We found that TME factors, such as regulatory T cells and adenosine, downregulated type I interferon receptor IFNAR1 on CD8 cytotoxic T lymphocytes (CTLs). These events relied upon poly-ADP ribose polymerase-11 (PARP11), which was induced in intratumoral CTLs and acted as a key regulator of the immunosuppressive TME. Ablation of PARP11 prevented loss of IFNAR1, increased CTL tumoricidal activity and inhibited tumor growth in an IFNAR1-dependent manner. Accordingly, genetic or pharmacologic inactivation of PARP11 augmented the therapeutic benefits of chimeric antigen receptor T cells. Chimeric antigen receptor CTLs engineered to inactivate PARP11 demonstrated a superior efficacy against solid tumors. These findings highlight the role of PARP11 in the immunosuppressive TME and provide a proof of principle for targeting this pathway to optimize immune therapies.
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http://dx.doi.org/10.1038/s43018-022-00383-0DOI Listing
May 2022

Pilot Cross-Sectional Quality of Life Study of a Diverse Endocrine Surgery Patient Population.

J Surg Res 2022 May 26;278:257-266. Epub 2022 May 26.

MedStar-Washington Hospital Center, Division of Endocrine Surgery, Washington, District of Columbia. Electronic address:

Introduction: Quality of life (QOL) studies of endocrine surgery patients have lacked diverse patient representation, long-term follow-up, or the use of validated questionnaires. This cross-sectional pilot study explored the need for prospective QOL studies in diverse endocrine surgery patients who were ≥6 mo postoperative.

Materials And Methods: In 2019, we mailed anonymous questionnaires to 671 adult patients cared for by an endocrine surgery division between 2018 and 2019. Patients were ≥6 mo postoperative and had undergone thyroidectomy, parathyroidectomy, or adrenalectomy. Patients mailed back responses to two validated questionnaires, the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and the Voice Handicap Index-10 (VHI-10). We compared responses across race.

Results: Of 135 respondents (20.1% response rate), 27.4% were 60-69 y and 69.6% were female. Race and ethnicity frequencies include 60.0% White patients, 27.4% Black patients, 4.4% Asian patients, and 5.2% Hispanic/LatinX patients. For surgery, 57.8% underwent thyroidectomy, 28.2% parathyroidectomy, 9.6% both, 4.4% adrenalectomy, and 32.6% surgery for cancer. Regarding PROMIS-29 results for patients who underwent thyroidectomy, significant differences were observed in the domains of physical function, depression, sleep disturbances, social roles, and global pain across race (P < 0.05). However, few differences were seen after completion of post hoc pairwise comparisons. We did not observe differences in PROMIS scores across race among patients who underwent parathyroidectomy and adrenalectomy or in VHI-10 for all surgical groups.

Conclusions: These results suggest long-term QOL differences across race and surgery type and support the need for prospective studies among diverse endocrine surgery patients.
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http://dx.doi.org/10.1016/j.jss.2022.04.068DOI Listing
May 2022

How Impulsiveness Influences Obesity: The Mediating Effect of Resting-State Brain Activity in the dlPFC.

Front Psychiatry 2022 10;13:873953. Epub 2022 May 10.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Impulsiveness is a stable personal characteristic that contributes to obesity and may interact with it. Specifically, obesity is caused by unrestrained impulse eating that is not consciously controlled and leads to a hormonal imbalance that also can impair impulse control. However, the mechanism of this relationship is unclear. In our study, 35 obese individuals (body mass index, BMI > 28) were recruited and matched with 31 healthy controls (BMI < 24) in age and education level. All the participants underwent a resting-state fMRI and completed the Barratt Impulsiveness Scale-11. The results showed that patients with obesity had a significantly lower fractional amplitude of low-frequency fluctuations (fALFF) in the bilateral dorsolateral prefrontal cortex (dlPFC) and higher fALFF in the left fusiform cortex. In addition, non-planning impulsiveness was positively correlated with BMI. Importantly, we found that the right dlPFC completely mediated the relationship between non-planning impulsiveness and BMI. Our findings suggest that impulsivity is statistically more likely to precede obesity than to precede impulsivity and contributes to obesity by downregulating spontaneous activity in the dlPFC. This suggests that the dlPFC, which is associated with executive control, may be able a potential target for treating obesity.
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http://dx.doi.org/10.3389/fpsyt.2022.873953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127259PMC
May 2022

Deconstructing the intra-tumor subclonal heterogeneity of lung synchronous ground-glass nodules using whole-genome sequencing.

Signal Transduct Target Ther 2022 05 27;7(1):164. Epub 2022 May 27.

State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.

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http://dx.doi.org/10.1038/s41392-022-00982-4DOI Listing
May 2022

Multiplex Fragment Analysis for Flexible Detection of All SARS-CoV-2 Variants of Concern.

Clin Chem 2022 May 25. Epub 2022 May 25.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge, and effective tracking requires rapid return of results. Surveillance of variants is typically performed by whole genome sequencing (WGS), which can be financially prohibitive and requires specialized equipment and bioinformatic expertise. Genotyping approaches are rapid methods for monitoring SARS-CoV-2 variants but require continuous adaptation. Fragment analysis may represent an approach for improved SARS-CoV-2 variant detection.

Methods: A multiplex fragment analysis approach (CoVarScan) was validated using PCR targeting variants by size and fluorescent color. Eight SARS-CoV-2 mutational hot spots in variants of concern (VOCs) were targeted. Three primer pairs (recurrently deleted region [RDR] 1, RDR2, and RDR3-4) flank RDRs in the S-gene. Three allele-specific primers target recurrent spike receptor binding domain mutants. Lastly, 2 primer pairs target recurrent deletions or insertions in ORF1A and ORF8. Fragments were resolved and analyzed by capillary electrophoresis (ABI 3730XL), and mutational signatures were compared to WGS results.

Results: We validated CoVarScan using 3544 clinical respiratory specimens. The assay exhibited 96% sensitivity and 99% specificity compared to WGS. The limit of detection for the core targets (RDR1, RDR2, and ORF1A) was 5 copies/reaction. Variants were identified in 95% of samples with cycle threshold (CT) <30 and 75% of samples with a CT 34 to 35. Assay design was frozen April 2021, but all subsequent VOCs have been detected including Delta (n = 2820), Mu, (n = 6), Lambda (n = 6), and Omicron (n = 309). Genotyping results are available in as little as 4 h.

Conclusions: Multiplex fragment analysis is adaptable and rapid and has similar accuracy to WGS to classify SARS-CoV-2 variants.
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http://dx.doi.org/10.1093/clinchem/hvac081DOI Listing
May 2022

Postintubation Sedation After a Formulary Change From Succinylcholine to Rocuronium in a Critical Care Transport Organization.

Air Med J 2022 May-Jun;41(3):287-291. Epub 2022 Mar 17.

Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Objective: Rocuronium is increasingly used as a first-line neuromuscular blocker (NMB) in rapid sequence intubation by transport teams. Prior work has shown that rocuronium is associated with a delay in postintubation sedation compared with intubation with succinylcholine.

Methods: Boston MedFlight is a consortium-based transport organization. In 2017, the intubation protocol and formulary for Boston MedFlight was changed to replace succinylcholine with rocuronium. We performed a retrospective review of patients intubated by the critical care transport teams from January 2017 through December 2019.

Results: We analyzed data for 264 intubations, 92 with succinylcholine and 172 with rocuronium. Ketamine and etomidate were the most common induction agents. The mean time from NMB administration to the first dose of sedation was 9.2 minutes (95% confidence interval, 5.4-23.7) for the succinylcholine cohort and 14.8 minutes (95% confidence interval, 8.4-38.0; P < .001) for the rocuronium cohort. After neuromuscular blockade, the total hourly weight-adjusted fentanyl dose was significantly lower for patients intubated with rocuronium compared with succinylcholine.

Conclusions: Intubation with rocuronium was associated with a longer time until the administration of sedation and decreased postneuromuscular blockade fentanyl administration compared with intubation with succinylcholine. These findings suggest opportunities for improvement in sedation and analgesia practices after rocuronium rapid sequence intubation.
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http://dx.doi.org/10.1016/j.amj.2022.02.009DOI Listing
May 2022

An Initial Evaluation of Human Plasma cMLC-1: A Potential Protein Biomarker for Trastuzumab-Induced Cardiotoxicity, Breast Cancer Screening and Progression.

Front Oncol 2022 3;12:809715. Epub 2022 May 3.

Division of Gastrointestinal and Oncologic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Background: Trastuzumab is a targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, trastuzumab-induced cardiotoxicity (TIC) has been reported when trastuzumab is administered to patients as a single agent or combined with anthracycline. Currently no means for detecting the early onset of TIC such as a protein biomarker is available. In this regard and based on promising results from a preliminary animal study, the potential of cardiac myosin light chain 1(cMLC-1) as a biomarker to predict TIC, screen patients for breast cancer and monitor tumor progression in breast cancer patients was evaluated.

Methods: Archived plasma samples collected before and after trastuzumab treatment at various fixed time points from 15 HER2 patients with or without cardiotoxicity, recently collected plasma samples from 79 breast cancer patients (40 HER2, 39 HER2), and 46 healthy donors were analyzed for cMLC-1 levels using an enzyme-linked immunosorbent assay (ELISA).

Results: An elevated plasma cMLC-1 level was found to be associated with TIC in 3 out of 7 (43%) trastuzumab-treated HER2 breast cancer patients. However, this study provided an opportunity for us to study plasma cMCL-1 levels in breast cancer patients. It was demonstrated that elevated plasma cMCL-1 is associated with breast cancer. The cutoff cMLC-1 concentration is estimated to be 44.99 ng/mL with a sensitivity of 59.49% (95%CI: 48.47%-69.63%) and specificity of 71.74% (95%CI: 57.45% -82.68%). We also found a noticeable but not significantly more elevated plasma cMCL-1 level in HER2 than in HER2 breast cancer patients with the given sample sizes. As a result, improved sensitivity of 79.49% (95%CI: 64.47%-89.22%) with the specificity of 63.04% (95%CI:48.60%-75.48%) were obtained for cMLC-1 to predict HER2 breast cancer with the cutoff at 37.17 ng/mL. Moreover, this study determined that cMLC-1 level was significantly higher in patients with metastatic breast cancer than in patients with non-metastatic breast cancer.

Conclusions: While the analysis of cMLC-1 levels in the plasma of a limited number of trastuzumab-treated HER2 breast cancer patients failed to fully support its identification as a blood protein biomarker for predicting TIC, additional analyses of plasma cMLC-1 levels did significantly establish its correlations with breast cancer and disease progression. Our findings shed light on and filled, to some extent, the gap of knowledge of the potential of cMLC-1 as a blood protein biomarker for screening breast cancer and monitoring disease progression of breast cancer.
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http://dx.doi.org/10.3389/fonc.2022.809715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113547PMC
May 2022

A Deep Learning Model Based on MRI and Clinical Factors Facilitates Noninvasive Evaluation of KRAS Mutation in Rectal Cancer.

J Magn Reson Imaging 2022 May 19. Epub 2022 May 19.

Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Recent studies showed the potential of MRI-based deep learning (DL) for assessing treatment response in rectal cancer, but the role of MRI-based DL in evaluating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation remains unclear.

Purpose: To develop a DL method based on T2-weighted imaging (T2WI) and clinical factors for noninvasively evaluating KRAS mutation in rectal cancer.

Study Type: Retrospective.

Subjects: A total of 376 patients (108 women [28.7%]) with histopathology-confirmed rectal adenocarcinoma and KRAS mutation status.

Field Strength/sequence: A 3 T, turbo spin echo T2WI and single-shot echo-planar diffusion-weighted imaging (b = 0, 1000 sec/mm ).

Assessment: A clinical model was constructed with clinical factors (age, gender, carcinoembryonic antigen level, and carbohydrate antigen 199 level) and MRI features (tumor length, tumor location, tumor stage, lymph node stage, and extramural vascular invasion), and two DL models based on modified MobileNetV2 architecture were evaluated for diagnosing KRAS mutation based on T2WI alone (image model) or both T2WI and clinical factors (combined model). The clinical usefulness of these models was evaluated through calibration analysis and decision curve analysis (DCA).

Statistical Tests: Mann-Whitney U test, Chi-squared test, Fisher's exact test, logistic regression analysis, receiver operating characteristic curve (ROC), Delong's test, Hosmer-Lemeshow test, interclass correlation coefficients, and Fleiss kappa coefficients (P < 0.05 was considered statistically significant).

Results: All the nine clinical-MRI characteristics were included for clinical model development. The clinical model, image model, and combined model in the testing cohort demonstrated good calibration and achieved areas under the curve (AUCs) of 0.668, 0.765, and 0.841, respectively. The combined model showed improved performance compared to the clinical model and image model in two cohorts. DCA confirmed the higher net benefit of the combined model than the other two models when the threshold probability is between 0.05 and 0.85.

Data Conclusion: The proposed combined DL model incorporating T2WI and clinical factors may show good diagnostic performance. Thus, it could potentially serve as a supplementary approach for noninvasively evaluating KRAS mutation in rectal cancer.

Evidence Level: 3 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.28237DOI Listing
May 2022

Nanohybrids that consisit of p-type, nitrogen-doped ZnO and graphene nanostructures: synthesis, photophysical properties, and biosensing application.

Nanotechnology 2022 Jun 7;33(34). Epub 2022 Jun 7.

Lab for Nanoelectronics and NanoDevices, Department of Electronics Science and Technology, Hangzhou Dianzi University, Hangzhou 310018, People's Republic of China.

ZnO, a promising material for optoelectronic applications, has attracted considerable attention due to its wide and direct band gap and large exciton binding energy. To understand the applications of this material, fabrication of high quality p-type ZnO is a key step. However, a reliable p-type doping of this material remains a major challenge. In this study, we report p-type nitrogen-doped ZnO nanoparticle, grown in a nitrogen doped graphene layer matrix by a plasma heating process using a natural protein and zinc nitrate as the precursors. The structural characterizations are developed by several microscopic techniques including the field emission electron microscopy, high resolution transmission electron microscopy, x-ray photoelectron spectroscopy, and micro-Raman analysis. In addition, the ultraviolet (UV)-visible absorption characteristics and photoluminescence properties of the samples are studied. Its p-type conduction behaviour is confirmed by the Hall effect measurement, which was ascribed to the high nitrogen dopant concentration in the Zn-poor ZnO, and the related mechanism for the p-type behaviour is also discussed. Moreover, the results of the glucose detection based on the strong green luminescence of glucose indicate that the nitrogen-doped ZnO nanodots/nitrogen-doped graphene layer nanohybrid is also a competitive candidate in the biosensing field.
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http://dx.doi.org/10.1088/1361-6528/ac70e4DOI Listing
June 2022

A diverse English keyword search reveals the value of scriptaid treatment for porcine embryo development following somatic cell nuclear transfer.

Reprod Fertil Dev 2022 May 18. Epub 2022 May 18.

Context: Incomplete epigenetic reprogramming of histone deacetylation (HDAC) is one of the main reasons for the low efficiency of somatic cell nuclear transfer (SCNT). Scriptaid is a synthetic HDAC inhibitor (HDACi) that may improve the efficiency of porcine SCNT.

Aims: This study aimed to determine whether scriptaid increases the number of blastocyst cells or the cleavage rate.

Methods: We conducted a meta-analysis of the pertinent literature published over the past decade.

Key Results: A total of 73 relevant papers were retrieved using a diverse English keyword search, and 11 articles were used for the meta-analysis. Scriptaid was positively correlated with blastocyst rate but had no effect on cleavage rate or blastocyst cell number. A subgroup analysis of blastocyst cell number showed that the staining method was the source of the heterogeneity.

Conclusions: In SCNT embryos, scriptaid treatment after activation can promote embryonic development, but there may be adverse effects on early development.

Implications: HDACi research should focus on SCNT birth efficiency.
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http://dx.doi.org/10.1071/RD22025DOI Listing
May 2022

Immunoregulation in Diabetic Wound Repair with a Photoenhanced Glycyrrhizic Acid Hydrogel Scaffold.

Adv Mater 2022 May 16:e2200521. Epub 2022 May 16.

School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

M1 macrophage accumulation and excessive inflammation are commonly encountered issues in diabetic wounds and can fail in the healing process. Hence, hydrogel dressings with immunoregulatory capacity have great promise in the clinical practice of diabetic wound healing. However, current immunoregulatory hydrogels are always needed for complex interventions and high-cost treatments, such as cytokines and cell therapies. In this study, a novel glycyrrhizic acid (GA)-based hybrid hydrogel dressing with intrinsic immunoregulatory properties is developed to promote rapid diabetic wound healing. This hybrid hydrogel consists of interpenetrating polymer networks composed of inorganic Zn -induced self-assembled GA and photo-crosslinked methyl acrylated silk fibroin (SF), realizing both excellent injectability and mechanical strength. Notably, the SF/GA/Zn hybrid hydrogel can regulate macrophage responses in the inflammatory microenvironment, circumventing the use of any additives. The immunomodulatory properties of the hydrogel can be harnessed for safe and efficient therapeutics that accelerate the three phases of wound repair and serve as a promising dressing for the management of diabetic wounds.
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http://dx.doi.org/10.1002/adma.202200521DOI Listing
May 2022

An unconventional vertical fluidic-controlled wearable platform for synchronously detecting sweat rate and electrolyte concentration.

Biosens Bioelectron 2022 Aug 10;210:114351. Epub 2022 May 10.

i-Lab, Key Laboratory of Multifunctional Nanomaterials and Smart Systems, Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences (CAS), 398 Ruoshui Road, Suzhou, Jiangsu, 215123, PR China; School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui, 230026, PR China; Vacuum Interconnected Nanotech Workstation (Nano-X), Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences (CAS), 385 Ruoshui Road, Suzhou, Jiangsu, 215123, PR China; Gusu Laboratory of Materials, 388 Ruoshui Road, Suzhou, Jiangsu, 215123, PR China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, PR China. Electronic address:

Epidermal microfluidic devices with long microchannels have been developed for continuous sweat analysis, which are crucial to assess personal hydration status and underlying health conditions. However, the flow resistance in long channels and the ionic concentration variation significantly affect the accuracy of both the sweat rate and electrolyte concentration measurements. Herein, we present a novel fluidic-controlled wearable platform for synchronously dropwise-detecting the sweat rate and total electrolyte concentration. The unconventional platform consisting of a vertically shortened channel, a pair of embedded electrodes and an absorption layer, is designed to minimize the flow resistance and transform sweat fluidics into uniform micro-droplets for chronological and dropwise detection. Real-time sweat conductance is decoupled from a square-wave-like curve, where the sweat rate and electrolyte concentration can be derived from the interval time and peak value, respectively. Flexible and wearable band devices are demonstrated to show their potential application for hydration status assessment during exercises.
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http://dx.doi.org/10.1016/j.bios.2022.114351DOI Listing
August 2022

Rising childhood income inequality and declining Americans' health.

Soc Sci Med 2022 Jun 7;303:115016. Epub 2022 May 7.

Duke University, USA.

Morbidity and mortality are on the rise among Baby Boomers and younger cohorts. This study investigates whether this unfavorable health trend across birth cohorts 1925-1999 is related to rising income inequality Americans face during childhood. We use two nationally representative datasets: National Health and Nutrition Examination Surveys (NHANES) 1988-2018 and Panel Studies of Income Dynamics (PSID) 1968-2013, and two health outcomes: biomarkers of physiological dysregulation, and a chronic disease index. Childhood income inequality is measured by the average of the Gini index at the national level each birth cohort is exposed to between birth and age 18, where the Gini index from 1925 to 2016 is computed based on Internal Revenue Service income data. By merging childhood income inequality to individual level data from NHANES or PSID based on birth cohort, we find childhood income inequality is positively associated with the risk of physiological dysregulation in adulthood for all gender and racial groups in the NHANES data. It is also significantly related to the risk of chronic disease in the PSID data. This association is robust to controls for individual level childhood health and family background, adulthood socioeconomic and marital status, and contemporary macro socioeconomic factors. More importantly, childhood income inequality exposure explains a substantial amount of variation in these two health outcomes across cohorts, a pattern not observed for other early life exposures that display negative temporal trends similar to those for childhood income inequality. This study provides important evidence that income inequality experienced during childhood may have a long-lasting negative consequence for adult health, which partially explains the adverse health trends experienced by Baby Boomers and younger cohorts in the United States.
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http://dx.doi.org/10.1016/j.socscimed.2022.115016DOI Listing
June 2022

A Partially Randomized Patient Preference Trial to Assess the Quality of Life and Patency Rate After Minimally Invasive Cardiac Surgery-Coronary Artery Bypass Grafting: Design and Rationale of the MICS-CABG PRPP Trial.

Front Cardiovasc Med 2022 25;9:804217. Epub 2022 Apr 25.

Department of Cardiac Surgery, Peking University Third Hospital, Beijing, China.

Background: Minimally invasive cardiac surgery-coronary artery bypass grafting (MICS-CABG) has emerged as a safe alternative to standard cardiac surgery. However, treatment preferences can decrease the generalizability of RCT results to the clinical population (i.e., reduce external validity) and influence adherence to the treatment protocol and study outcomes (i.e., reduce internal validity). However, this has not yet been properly investigated in randomized trials with consideration of treatment preferences.

Study Design: In this study, patients with a preference will be allocated to treatment strategies accordingly, whereas only those patients without a distinct preference will be randomized. The randomized trial is a 248-patient controlled, randomized, investigator-blinded trial. It is designed to compare whether treatment with MICS-CABG is beneficial in comparison to CABG. This study is aimed to establish the superiority hypothesis for the physical component summary (PCS) accompanied by the non-inferiority hypothesis for overall graft patency. Patients with no treatment preference will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoints are the PCS score at 30 days after surgery and the overall patency rate of the grafts within 14 days after surgery. Secondary outcome measures include the PCS score and patency rate at different time points. Safety endpoints include major adverse cardiac and cerebrovascular events, complications, bleeding, wound infection, death, etc.

Conclusions: This trial will address essential questions of the efficacy and safety of MICS-CABG. The study will also address the impact of patients' preferences on external validity and internal validity.
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http://dx.doi.org/10.3389/fcvm.2022.804217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081498PMC
April 2022

Spatial distribution and risk assessment of metal(loid)s in marine sediments in the Arctic Ocean and Bering Sea.

Mar Pollut Bull 2022 Jun 7;179:113729. Epub 2022 May 7.

School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China. Electronic address:

Seventy-four surface sediment samples were collected from the Arctic Ocean and Bering Sea to determine the content of metal(loid)s (As, Cu, Cd, Ni, Pb, Zn and Cr). Metal(loid)s content in these sediments varied from 2.36-41.90 mg/kg for As, 8.63-82.28 mg/kg for Cu, 0.14-0.71 mg/kg for Cd, 11.86-100.60 mg/kg for Ni, 8.30-27.58 mg/kg for Pb, 39.93-391.43 mg/kg for Zn, and 40.96-106.49 mg/kg for Cr. The pH and water-soluble organic carbon content had considerable impacts on the content of metal(loid)s in sediment, but the texture of sediment has limited influence on metal(loid)s content in sediment. In addition, the hotspots of most of these metal(loid)s appeared in the Beaufort Sea region. The geoaccumulation index (I) indicated that Cd was the metal with the highest contamination in these sediments, with 55.41% of the sample sites posing moderate pollution. The ecological risk for As, Cu, Ni, Pb, Zn and Cr indicates low ecological risk (100%), while Cd posed moderate risk (35.14%), considerable risk (54.05%) and high risk (10.81%) and attributed more than 76.45% of the total potential ecological risk of these metal(loid)s.
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http://dx.doi.org/10.1016/j.marpolbul.2022.113729DOI Listing
June 2022

Contribution of local and surrounding area anthropogenic emissions to a high ozone episode in Zhengzhou, China.

Environ Res 2022 Sep 6;212(Pt C):113440. Epub 2022 May 6.

Key Laboratory of Geospatial Technology for the Middle and Lower Yellow River Regions (Henan University), Ministry of Education, Kaifeng, Henan, 475004, China; Henan Key Laboratory of Integrated Air Pollution Control and Ecological Security, Henan University, Kaifeng, Henan, 475004, China. Electronic address:

This study analyzed an ozone pollution episode that occurred in the summer of 2020 in Zhengzhou, the provincial capital of Henan, China, and quantified the contribution of local and surrounding area anthropogenic emissions to this episode based on the Weather Research and Forecasting with Chemistry (WRF/Chem) model. Simulation results showed that the WRF/Chem model is well suited to simulate the ozone concentrations in this area. In addition, four simulation scenarios (removing the emissions from the northern Zhengzhou, southwestern Zhengzhou, Zhengzhou local and southeastern Zhengzhou) were conducted to explore the specific contributions of local emissions and emissions from surrounding areas within Henan to this ozone pollution episode. We found that contributions from the northern, local, southwestern, and southeastern regions were 6.1%, 5.9%, 1.7%, and 1.5%, respectively. The northern and local emissions of Zhengzhou (only emissions from Zhengzhou) were prominent contributors within the simulation areas. In other words, during this episode, most of the ozone pollution in Zhengzhou appeared to be transported in from regions outside Henan Province.
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http://dx.doi.org/10.1016/j.envres.2022.113440DOI Listing
September 2022

A high-dosage microneedle for programmable lidocaine delivery and enhanced local long-lasting analgesia.

Mater Sci Eng C Mater Biol Appl 2021 Dec 23:112620. Epub 2021 Dec 23.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

Considering the staggering global prevalence of local pain affecting hundreds of million individuals, it is of great significance to develop advanced dosage forms or delivery systems for analgesic therapy to fulfill clinical applicability. In this study, a hydrogel microneedles (MNs) system made out of gelatin-methacryloyl (GelMA) was designed to deliver lidocaine hydrochloride (LiH) in a sustained manner, and the drug loading capacity of the GelMA MNs was increased considerably by using the backing layer reservoir. The in vitro and in vivo tests showed that the fabricated GelMA MNs are strong enough for reliable skin application, and achieve high drug delivery efficiency as compared with the commercial lidocaine patches. The Spared-nerve injury (SNI) model of rats was also prepared to test behavioral pain sensitivity in response to mechanical stimuli, which proved that the LiH/GelMA MNs can enhance and prolong the anesthetic effect of LiH. In addition, with biosafety evaluation in rats, the MNs treated site restored to normal appearance within several hours of application and no dermatosis-related side effects or behavior disorders were observed during the experiment. Together these results indicated that the use of GelMA MNs for transdermal delivery of LiH is an effective, safe and simple treatment method to provide a better choice for local long-lasting analgesia.
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http://dx.doi.org/10.1016/j.msec.2021.112620DOI Listing
December 2021

Proteotoxic stress disrupts epithelial integrity by inducing MTOR sequestration and autophagy overactivation.

Autophagy 2022 May 6:1-15. Epub 2022 May 6.

Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.

Macroautophagy/autophagy, an evolutionarily conserved degradation system, serves to clear intracellular components through the lysosomal pathway. Mounting evidence has revealed cytoprotective roles of autophagy; however, the intracellular causes of overactivated autophagy, which has cytotoxic effects, remain elusive. Here we show that sustained proteotoxic stress induced by loss of the NG and lch repeat-containing protein C53A5.6/RIKE-1 induces sequestration of LET-363/MTOR complex and overactivation of autophagy, and consequently impairs epithelial integrity in . In C53A5.6/RIKE-1-deficient animals, blocking autophagosome formation effectively prevents excessive endosomal degradation, mitigates mislocalization of intestinal membrane components and restores intestinal lumen morphology. However, autophagy inhibition does not affect LET-363/MTOR aggregation in animals with compromised C53A5.6/RIKE-1 function. Improving proteostasis capacity by reducing DAF-2 insulin/IGF1 signaling markedly relieves the aggregation of LET-363/MTOR and alleviates autophagy overactivation, which in turn reverses derailed endosomal trafficking and rescues epithelial morphogenesis defects in C53A5.6/RIKE-1-deficient animals. Hence, our studies reveal that C53A5.6/RIKE-1-mediated proteostasis is critical for maintaining the basal level of autophagy and epithelial integrity. ACT-5: actin 5; ACTB: actin beta; ALs: autolysosomes; APs: autophagosomes; AJM-1: apical junction molecule; ATG: autophagy related; C. elegans: Caenorhabditis elegans; CPL-1: cathepsin L family; DAF: abnormal dauer formation; DLG-1: Drosophila discs large homolog; ERM-1: ezrin/radixin/moesin; EPG: ectopic P granule; GFP: freen fluorescent protein; HLH-30: helix loop helix; HSP: heat shock protein; LAAT-1: lysosome associated amino acid transporter; LET: lethal; LGG-1: LC3, GABARAP and GATE-16 family; LMP-1: LAMP (lysosome-associated membrane protein) homolog; MTOR: mechanistic target of rapamycin kinase; NUC-1: abnormal nuclease; PEPT-1/OPT-2: Peptide transporter family; PGP-1: P-glycoprotein related; RAB: RAB family; RIKE-1: RING and Kelch repeat-containing protein; SLCF-1: solute carrier family; SQST-1: sequestosome related; SPTL-1: serine palmitoyl transferase family.
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http://dx.doi.org/10.1080/15548627.2022.2071381DOI Listing
May 2022

Correction to: miR-495-3p depresses cell proliferation and migration by downregulating HMGB1 in colorectal cancer.

World J Surg Oncol 2022 Apr 30;20(1):138. Epub 2022 Apr 30.

Department of Oncology, The First Afliated Hospital of Wannan Medical College, Wuhu, 241002, China.

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http://dx.doi.org/10.1186/s12957-022-02589-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055694PMC
April 2022

Structure, phase transition and properties of the one-dimensional antiferromagnet Cu(2,6-dimethylpyrazine)Br.

RSC Adv 2021 Jun 25;11(37):22565-22570. Epub 2021 Jun 25.

School of Physics and Optoelectronic Engineering, Ludong University Yantai Shandong 264025 China

We report the crystal structure and properties of the one-dimensional = 1/2 antiferromagnet Cu(2,6-dimethylpyrazine)Br with strong intra-chain exchange. At room temperature, its linear spin chains are formed by Cu ions the non-bonding Br⋯Br contacts. Interestingly, a phase transition from to 21/ structure occurs at ≈ 248 K below which the [CuBr] spin chains become non-linear and the magnetic susceptibility abruptly increases, reflecting the weakening of antiferromagnetic exchange strength. This result evidences the Goodenough-Kanamori rules which claim that a linear super-exchange pathway produces stronger antiferromagnetic coupling. From magnetic susceptibility measurements we find the average intra-chain exchange strength is / ≈ -88.18 K in the low temperature phase. Both magnetic and specific measurements show the absence of magnetic ordering down to 2 K, implying the excellent magnetic one-dimensionality of Cu(2,6-dimethylpyrazine)Br. We also performed ultra-violet (UV) absorption and photoluminescence measurements which give a semiconducting band gap ≈ 2.79 eV which is consistent with theoretical calculations.
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http://dx.doi.org/10.1039/d1ra02318gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034352PMC
June 2021
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