bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolactin Inducible Protein, but Not Prolactin, Is Present in Human Tears, Is Involved in Tear Film Quality, and Influences Evaporative Dry Eye Disease
Authors: Jüngert Katharina , Paulsen Friedrich , Jacobi Christina , Horwath-Winter Jutta , Garreis Fabian
Published: June 2022

Purpose

Decreased production of the aqueous component of the tear film is an important cause of the development of dry eye disease (DED). Tear production is influenced by hormones and hormone-like factors. Prolactin (PLR), a multifunctional pituitary gland hormone, is regularly present in the lacrimal gland of rats and rabbits. In humans, serum PLR concentration correlates with tear quality. To gain deeper insights of possible effects of PRL, prolactin receptor (PRLR) and prolactin inducible protein (PIP), we analyzed the three proteins in the human lacrimal apparatus and in reflex tears of healthy volunteers as well as patients suffering from DED.

Methods

Gene expression of PRLR and PIP was analyzed by RT-PCR in cadaveric human lacrimal gland and ocular surface tissues, immortalized human corneal epithelial cells (HCE and hTEPI) and human Meibomian gland epithelial cells (HMGECs). At the protein level, the expression and localization of PRL, PRLR and PIP in formalin-fixed paraffin sections of the lacrimal apparatus were studied by immunohistochemistry. In addition, tear fluid from DED patients and healthy volunteers was analyzed by ELISA to determine the concentration of PRL and PIP.

Results

RT-PCR analyses revealed gene expression of PRLR and PIP in human tissue samples of cornea, lacrimal glands, and eyelids, whereas only PIP, but not PRLR, was detectable in immortalized corneal epithelial cells. Immunohistochemistry revealed for the first time the expression and localization of PRL, PRLR, and PIP in human tissues of the lacrimal apparatus and at the ocular surface. PRL and PRLR were detectable in corneal epithelium, lacrimal glands, and Meibomian glands. Reflex tears from DED patients revealed significantly increased PIP concentrations, whereas PRL was undetectable in tears of DED patients and healthy volunteers.

Conclusion

PRL, PRLR, and PIP are found in the lacrimal apparatus and on the ocular surface. PIP, but not PRL, is present in human tears and appears to be involved in the physiology of tear film quality. Our clinical data revealed that PIP may affect tear quality, but further functional analyses are needed to fully elucidate the effects of PRL and PIP-associated factors in tear secretion as well as in the connection of DED.
Brain Histology and Immunohistochemistry After Resuscitation From Hemorrhagic Shock in Swine With Pre-Existing Atherosclerosis and Sodium Thiosulfate (Na2S2O3) Treatment
Authors: Denoix Nicole , McCook Oscar , Scheuerle Angelika , Kapapa Thomas , Hoffmann Andrea , Gündel Harald , Waller Christiane , Szabo Csaba , Radermacher Peter , Merz Tamara
Published: June 2022

Background

The hydrogen sulfide (H2S) and the oxytocin/oxytocin receptor (OT/OTR) systems interact in the central nervous and cardiovascular system. As a consequence of osmotic balance stress, H2S stimulates OT release from the paraventricular nuclei (PVN) in the hypothalamic regulation of blood volume and pressure. Hemorrhagic shock (HS) represents one of the most pronounced acute changes in blood volume, which, moreover, may cause at least transient brain tissue hypoxia. Atherosclerosis is associated with reduced vascular expression of the main endogenous H2S producing enzyme cystathionine-γ-lyase (CSE), and, hence, exogenous H2S administration could be beneficial in these patients, in particular after HS. However, so far cerebral effects of systemic H2S administration are poorly understood. Having previously shown lung-protective effects of therapeutic Na2S2O3 administration in a clinically relevant, long-term, porcine model of HS and resuscitation we evaluated if these protective effects were extended to the brain.

Methods

In this study, available unanalyzed paraffin embedded brain sections (Na2S2O3N = 8 or vehicle N = 5) of our recently published HS study were analyzed via neuro-histopathology and immunohistochemistry for the endogenous H2S producing enzymes, OT, OTR, and markers for brain injury and oxidative stress (glial fibrillary acidic protein (GFAP) and nitrotyrosine).

Results

Neuro-histopathological analysis revealed uninjured brain tissue with minor white matter edema. Protein quantification in the hypothalamic PVN showed no significant inter-group differences between vehicle or Na2S2O3 treatment.

Conclusions

The endogenous H2S enzymes, OT/OTR co-localized in magnocellular neurons in the hypothalamus, which may reflect their interaction in response to HS-induced hypovolemia. The preserved blood brain barrier (BBB) may have resulted in impermeability for Na2S2O3 and no inter-group differences in the PVN. Nonetheless, our results do not preclude that Na2S2O3 could have a therapeutic benefit in the brain in an injury that disrupts the BBB, e.g., traumatic brain injury (TBI) or acute subdural hematoma (ASDH).
Preliminary Proof-of-Concept Testing of Novel Antimicrobial Heat-Conducting “Metallic” Coatings Against Biofouling and Biocorrosion
Authors: Wang Di , Hall Timothy D. , Gu Tingyue
Published: June 2022

NiMo (nickel-molybdenum) and NiMo with embedded CeO2 nanoparticles (NPs; 100 nm) were tested as antimicrobial coatings (~15 μm thickness) on titanium (Ti) surfaces using an electrochemical process for heat exchanger applications onboard marine vessels. Preliminary static biofouling and biocorrosion (also known as microbiologically influenced corrosion) assessments were carried out in glass bottles using pure-culture Desulfovibrio vulgaris, a sulfate-reducing bacterium (SRB), in deoxygenated ATCC 1249 medium at 37°C, and using an alga (Chlorella vulgaris) mixed with general heterotrophic bacteria (GHB) in enriched artificial seawater at 28°C. It was found that the coating containing NiMo/CeO2 NPs were much more effective than NiMo in preventing SRB biofilm formation with an efficacy of 99% reduction in D. vulgaris sessile cells after 21 day incubation. The coating also exhibited a 50% lower corrosion current density compared to the uncoated Ti against SRB corrosion. Both NiMo and NiMo/CeO2 NP coatings achieved 99% reduction in sessile algal cells. Confocal laser scanning microscopy (CLSM) biofilm images indicated a large reduction of sessile GHB cells. The CLSM images also confirmed the biocidal kill effects of the two coatings. Unlike polymer coatings, the “metallic” coatings are heat conductive. Thus, the corrosion resistant antifouling coatings are suitable for heat exchanger applications.
Vinegar Volatile Organic Compounds: Analytical Methods, Constituents, and Formation Processes
Authors: Xie Zhenzhen , Koysomboon Chanisara , Zhang Huan , Lu Zhenming , Zhang Xiuyan , Chen Fusheng
Published: June 2022

Vinegar is an acid condiment shared all over the world. According to the raw materials, vinegar can be mainly divided into fruit and cereal ones, both of which possess unique aroma and flavor characteristics and corresponding volatile organic compounds (VOCs). Many studies about vinegar VOCs' (VVOCs) sorts, analytical methods, and forming mechanisms have been done. In this review, the main categories of vinegar and their distribution in the world are briefly introduced, then VVOCs' analytical and identified methods, types, and forming processes are summarized. Additionally, the VVOCs' research directions are discussed and prospected. According to the searched literatures, this study is the first to systematically review the analytical methods, sorts, and formation mechanisms of VVOCs, which will make the readers better understand the vinegar's aromas and flavors and their producing mechanisms.
Divergent Reassortment and Transmission Dynamics of Highly Pathogenic Avian Influenza A(H5N8) Virus in Birds of China During 2021
Authors: Ye Hejia , Zhang Jiahao , Sang Yunfen , Shan Nan , Qiu Weihong , Zhong Wenting , Li Junbao , Yuan Zhaoxia
Published: June 2022

Highly pathogenic influenza A(H5N8) viruses had caused several outbreaks among wild bird and poultry populations across the globe, and strikingly, caused human infection, posing serious public health concerns. In this study, we conducted influenza surveillance in China during 2021 to monitor the evolution of influenza viruses in poultry. A total of 35 influenza viruses were obtained in chickens, ducks, and geese, of which 30 H5N8 viruses, 3 H5N1 viruses, and 2 H5N6 viruses. Phylogenetic analysis suggested all of H5N1, H5N6, and H5N8 isolates were derived from clade 2.3.4.4b H5N8 viruses during 2020/21 season, and notably, the internal genes of H5N1 and H5N6 viruses shared different genetic heterogeneity with H5N8 viruses and had been reassorted with wild bird-origin H5N1 viruses from Europe. By contrast, almost all H5N8 viruses exhibited only one phylogenic cluster with wild bird-origin H5N8 viruses in China and Korea, indicating that H5N8 viruses in China were more stable. Besides, we found that Korea is the main output geographic location in the spread of these H5N8 viruses to northern and eastern China, and especially, the co-circulation of H5N8 viruses occurred within China, with central China acted as a seeding population during the H5N8 epidemic. The statistical support was strong for viral migration from wild birds to chickens and ducks, indicating that 2.3.4.4b poultry-origin H5N8 viruses during 2020–2021 were originated from wild birds. Our findings provide novel insights into evolution and transmission dynamics of H5 subtype influenza viruses among poultry after novel H5N8 viruses invaded China for nearly one year.
Coexistence of Heavy Metal Tolerance and Antibiotic Resistance in Thermophilic Bacteria Belonging to Genus Geobacillus
Authors: Najar Ishfaq Nabi , Das Sayak , Kumar Santosh , Sharma Prayatna , Mondal Krishnendu , Sherpa Mingma Thundu , Thakur Nagendra
Published: June 2022

Hot springs are thought to be potential repositories for opportunistic infections, such as antibiotic-resistant strains. However, there is a scarcity of information on the mechanisms of antibiotic resistance gene (ARG) uptake, occurrence, and expression in thermophilic bacteria. Furthermore, because the genesis and proliferation of ARGs in environmental microorganisms are unknown, the research on antibiotic resistance profiles and probable mechanisms in thermophilic bacteria will become increasingly important. The goals of this study are to explore bacterial diversity, antibiotic and heavy metal resistance, and the prevalence and presence of ARG and metal resistance gene (MRG) in Geobacillus species. The 16S rRNA sequencing was used to determine the culturable bacterium diversity of 124 isolates. Standard Kirby Bauer Disc Diffusion and tube dilution procedures were used to determine antibiotic sensitivity and minimum inhibitory concentration (MIC). The tube dilution method was also used to check metal tolerance. To detect ARG and heavy MRG (HMRG), whole genome sequencing studies of the type species of the genus Geobacillus and five randomly selected Geobacillus species were performed. Graph Pad Prism and XLSTAT were used to perform statistical analyses such as ANOVA, EC50 analysis, and principal component analysis (PCA). The phylum Firmicutes and the genus Geobacillus dominated the culture-dependent bacterial diversity. Surprisingly, all thermophilic isolates, i.e., Geobacillus species, were sensitive to at least 10 different antibiotics, as evidenced by the lack of ARGs in whole genome sequencing analysis of numerous Geobacillus species. However, some of these isolates were resistant to at least five different heavy metals, and whole genome sequencing revealed the presence of MRGs in these thermophilic bacteria. The thermophilic genus Geobacillus is generally antibiotic sensitive, according to this study. In contrast, heavy metal is tolerated by them. As a result, it is possible that ARGs and MRGs do not coexist in these bacteria living in hot springs.
Co-infection of Fusarium aglaonematis sp. nov. and Fusarium elaeidis Causing Stem Rot in Aglaonema modestum in China
Authors: Zhang Yunxia , Chen Chao , Mai Zhanglong , Lin Jieying , Nie Liting , Maharachchikumbura Sajeewa S. N. , You Chunping , Xiang Meimei , Hyde Kevin D. , Manawasinghe Ishara S.
Published: June 2022

Aglaonema modestum (A. modestum) (Araceae) is an evergreen herbage, which is intensively grown as an ornamental plant in South China. A new disease was observed in A. modestum from 2020 to 2021 in Guangdong province, China. The disease symptoms associated with plants were initial leaf wilt, stem rot, and resulting plant death, leading to severe economic losses. In total, six Fusarium isolates were obtained from diseased plants. The putative pathogen was identified using both morphological characteristics and molecular phylogenetic analysis of calmodulin A (cmdA), RNA polymerase largest subunit 1 (rpb1), RNA polymerase II (rpb2), translation elongation factor-1α (tef1-α), and beta-tubulin (β-tubulin) sequences. Two Fusarium species were identified, namely, one new species, Fusarium aglaonematis (F. aglaonematis) belonging to Fusarium fujikuroi species complex. In addition, Fusarium elaeidis (F. elaeidis) belonging to the Fusarium oxysporum (F. oxysporum) species complex was also identified. Pathogenicity assays were conducted by inoculating each species into potted A. modestum plants and co-inoculating two species. The results showed that two Fusarium species could infect plants independently and can infect them together. Co-infection of these two species enhanced the disease severity of A. modestum. Compared to single inoculation of F. elaeidis, severity was higher and disease development was quicker when plants were only inoculated with F. aglaonematis. In addition, these two Fusarium species could infect Aglaonema plants without wounds, while inoculation with a physical injury increased disease severity. This is the first report of co-infection by F. aglaonematis and F. elaeidis causing stem rot on A. modestum worldwide. This study will be an addition to the knowledge of Fusarium diseases in ornamental plants. These results will provide a baseline to identify and control diseases associated with A. modestum.
Identification and Validation of a Novel Tumor Microenvironment-Related Prognostic Signature of Patients With Hepatocellular Carcinoma
Authors: Li Rui , Zhao Weiheng , Liang Rui , Jin Chen , Xiong Huihua
Published: June 2022

Background: In recent years, immunotherapy has changed the therapeutic landscape of hepatocellular carcinoma (HCC). Since the efficacy of immunotherapy is closely related to the tumor microenvironment (TME), in this study, we constructed a prognostic model based on TME to predict the prognosis and immunotherapy effect of HCC patients.

Methods: Transcriptome and follow-up data of 374 HCC patients were acquired from the TCGA Cancer Genome Atlas (TCGA) database. The immune/stromal/estimate scores (TME scores) and tumor purity were calculated using the ESTIMATE algorithm and the module most associated with TME scores were screened by the weighted gene co-expression network analysis (WGCNA). A TME score-related prognostic model was constructed and patients were divided into a high-risk group and a low-risk group. Kaplan-Meier survival curves and receiver operator characteristic curve (ROC) were used to evaluate the performance of the TME risk prognostic model and validated with the external database International Cancer Genome Consortium (ICGC) cohort. Combined with clinicopathologic factors, a prognostic nomogram was established. The nomogram’s ability to predict prognosis was assessed by ROC, calibration curve, and the decision curve analysis (DCA). Gene Set Enrichment Analyses (GSEA) were conducted to explore the underlying biological functions and pathways of this risk signature. Moreover, the possible correlation of risk signature with TME immune cell infiltration, immune checkpoint inhibitor (ICI) treatment response, single-nucleotide polymorphisms (SNPs), and drug sensitivity were assessed. Finally, real-time PCR was used to verify the gene expression levels in normal liver cells and cancer cells.

Results: KM survival analysis results indicated that high immune/stromal/estimate score groups were closely associated with a better prognosis, while the tumor purity showed a reverse trend (p < 0.01). WGCNA demonstrated that the yellow module was significantly correlated with the TME score. The 5-genes TME risk signature was built to predict the prognosis of patients with HCC including DAB2, IL18RAP, RAMP3, FCER1G, and LHFPL2. Patients with a low-risk score have higher levels of tumor-infiltrating immune cells and higher expression of immune checkpoints, which may be more sensitive to immunotherapy.

Conclusion: It provided a theoretical basis for predicting the prognosis and personalized treatment of patients with HCC.
Comparative Analysis of Dopaminergic and Cholinergic Mechanisms of Sensory and Sensorimotor Gating in Healthy Individuals and in Patients With Schizophrenia
Authors: Proshin Andrey T.
Published: June 2022

Sensory and sensorimotor gating provide the early processing of information under conditions of rapid presentation of multiple stimuli. Gating deficiency is observed in various psychopathologies, in particular, in schizophrenia. However, there is also a significant proportion of people in the general population with low filtration rates who do not show any noticeable cognitive decline. The review article presents a comparative analysis of existing data on the peculiarities of cholinergic and dopaminergic mechanisms associated with lowering gating in healthy individuals and in patients with schizophrenia. The differences in gating mechanisms in cohorts of healthy individuals and those with schizophrenia are discussed.
Prediction of Long-Term Restenosis After Carotid Endarterectomy Using Quantitative Magnetic Resonance Angiography
Authors: Andereggen Lukas , Amin-Hanjani Sepideh , Beck Jürgen , Luedi Markus M. , Gralla Jan , Schubert Gerrit A. , Tortora Angelo , Andres Robert H. , Arnold Marcel , Raabe Andreas , Reinert Michael
Published: June 2022

Background

To detect restenosis after carotid endarterectomy (CEA), long-term monitoring is required. However, non-selective follow-up is controversial and can be limited by costs and logistical considerations.

Objective

To examine the value of immediate perioperative vessel flow measurements after CEA using quantitative magnetic resonance angiography (QMRA) to detect patients at risk of long-term restenosis.

Methods

A prospective cohort study with long-term sonographic follow-up after CEA for symptomatic internal carotid artery stenosis (ICAs) > 50%. In all patients, vessel flow has been assessed both pre- and postoperatively using QMRA within ±3 days of surgery. Data on QMRA assessment were analyzed to identify patients at risk of restenosis for up to 10 years.

Results

Restenosis was recorded in 4 of 24 patients (17%) at a median follow-up of 6.8 ± 2.6 years. None of them experienced an ischemic event. Perioperative flow differences were significantly greater in patients without long-term restenosis, both for the ipsilateral ICA (p < 0.001) and MCA (p = 0.03), compared to those with restenosis (p = 0.22 and p = 0.3, respectively). The ICA mean flow ratio (p = 0.05) tended to be more effective than the MCA ratio in predicting restenosis over the long term (p = 0.35).

Conclusion

Our preliminary findings suggest that QMRA-based mean flow increases after CEA may be predictive of restenosis over the long term. Perioperative QMRA assessment could become an operator-independent screening tool to identify a subgroup of patients at risk for restenosis, in whom long-term monitoring is advised.
Early Changes in the White Matter Microstructure and Connectome Underlie Cognitive Deficit and Depression Symptoms After Mild Traumatic Brain Injury
Authors: Huang Wenjing , Hu Wanjun , Zhang Pengfei , Wang Jun , Jiang Yanli , Ma Laiyang , Zheng Yu , Zhang Jing
Published: June 2022

Cognitive and emotional impairments are frequent among patients with mild traumatic brain injury (mTBI) and may reflect alterations in the brain structural properties. The relationship between microstructural changes and cognitive and emotional deficits remains unclear in patients with mTBI at the acute stage. The purpose of this study was to analyze the alterations in white matter microstructure and connectome of patients with mTBI within 7 days after injury and investigate whether they are related to the clinical questionnaires. A total of 79 subjects (42 mTBI and 37 healthy controls) underwent neuropsychological assessment and diffusion-tensor MRI scan. The microstructure and connectome of white matter were characterized by tract-based spatial statistics (TBSSs) and graph theory approaches, respectively. Mini-mental state examination (MMSE) and self-rating depression scale (SDS) were used to evaluate the cognitive function and depressive symptoms of all the subjects. Patients with mTBI revealed early increases of fractional anisotropy in most areas compared with the healthy controls. Graph theory analyses showed that patients with mTBI had increased nodal shortest path length, along with decreased nodal degree centrality and nodal efficiency, mainly located in the bilateral temporal lobe and right middle occipital gyrus. Moreover, lower nodal shortest path length and higher nodal efficiency of the right middle occipital gyrus were associated with higher SDS scores. Significantly, the strength of the rich club connection in the mTBI group decreased and was associated with the MMSE. Our study demonstrated that the neuroanatomical alterations of mTBI in the acute stage might be an initial step of damage leading to cognitive deficits and depression symptoms, and arguably, these occur due to distinct mechanisms.
Comparing In-ear EOG for Eye-Movement Estimation With Eye-Tracking: Accuracy, Calibration, and Speech Comprehension
Authors: Skoglund Martin A. , Andersen Martin , Shiell Martha M. , Keidser Gitte , Rank Mike Lind , Rotger-Griful Sergi
Published: June 2022

This presentation details and evaluates a method for estimating the attended speaker during a two-person conversation by means of in-ear electro-oculography (EOG). Twenty-five hearing-impaired participants were fitted with molds equipped with EOG electrodes (in-ear EOG) and wore eye-tracking glasses while watching a video of two life-size people in a dialog solving a Diapix task. The dialogue was directionally presented and together with background noise in the frontal hemisphere at 60 dB SPL. During three conditions of steering (none, in-ear EOG, conventional eye-tracking), participants' comprehension was periodically measured using multiple-choice questions. Based on eye movement detection by in-ear EOG or conventional eye-tracking, the estimated attended speaker was amplified by 6 dB. In the in-ear EOG condition, the estimate was based on one selected channel pair of electrodes out of 36 possible electrodes. A novel calibration procedure introducing three different metrics was used to select the measurement channel. The in-ear EOG attended speaker estimates were compared to those of the eye-tracker. Across participants, the mean accuracy of in-ear EOG estimation of the attended speaker was 68%, ranging from 50 to 89%. Based on offline simulation, it was established that higher scoring metrics obtained for a channel with the calibration procedure were significantly associated with better data quality. Results showed a statistically significant improvement in comprehension of about 10% in both steering conditions relative to the no-steering condition. Comprehension in the two steering conditions was not significantly different. Further, better comprehension obtained under the in-ear EOG condition was significantly correlated with more accurate estimation of the attended speaker. In conclusion, this study shows promising results in the use of in-ear EOG for visual attention estimation with potential for applicability in hearing assistive devices.
Liver Transcriptome and Gut Microbiome Analysis Reveals the Effects of High Fructose Corn Syrup in Mice
Authors: Shen Yu , Sun Yangying , Wang Xiaoli , Xiao Yingping , Ma Lingyan , Lyu Wentao , Zheng Zibin , Wang Wen , Li Jinjun
Published: June 2022

High fructose corn syrup (HFCS) is a viscous mixture of glucose and fructose that is used primarily as a food additive. This article explored the effect of HFCS on lipid metabolism-expressed genes and the mouse gut microbiome. In total, ten 3-week-old male C57BL/6J mice were randomly divided into two groups, including the control group, given purified water (Group C) and 30% HFCS in water (Group H) for 16 weeks. Liver and colonic content were collected for transcriptome sequencing and 16S rRNA gene sequencing, respectively. HFCS significantly increased body weight, epididymal, perirenal fat weight in mice (p < 0.05), and the proportion of lipid droplets in liver tissue. The expression of the ELOVL fatty acid elongase 3 (Elovl3) gene was reduced, while Stearoyl-Coenzyme A desaturase 1 (Scd1), peroxisome proliferator activated receptor gamma (Pparg), fatty acid desaturase 2 (Fads2), acyl-CoA thioesterase 2 (Acot2), acyl-CoA thioesterase 2 (Acot3), acyl-CoA thioesterase 4 (Acot4), and fatty acid binding protein 2 (Fabp2) was increased in Group H. Compared with Group C, the abundance of Firmicutes was decreased in Group H, while the abundance of Bacteroidetes was increased, and the ratio of Firmicutes/Bacteroidetes was obviously decreased. At the genus level, the relative abundance of Bifidobacterium, Lactobacillus, Faecalibaculum, Erysipelatoclostridium, and Parasutterella was increased in Group H, whereas that of Staphylococcus, Peptococcus, Parabacteroides, Donghicola, and Turicibacter was reduced in Group H. Pparg, Acot2, Acot3, and Scd1 were positively correlated with Erysipelatoclostridium and negatively correlated with Parabacteroides, Staphylococcus, and Turicibacter. Bifidobacterium was negatively correlated with Elovl3. Overall, HFCS affects body lipid metabolism by affecting the expression of lipid metabolism genes in the liver through the gut microbiome.
Melatonin Alleviates Chilling Injury Symptom Development in Mango Fruit by Maintaining Intracellular Energy and Cell Wall and Membrane Stability
Authors: Bhardwaj Renu , Aghdam Morteza Soleimani , Arnao Marino Bañon , Brecht Jeffrey K. , Fawole Olaniyi Amos , Pareek Sunil
Published: June 2022

The efficacy of the signaling molecule melatonin for alleviating chilling injury (CI) in mango (Mangifera indica L.) fruit was studied to investigate the potential role of membrane integrity, energy charge, and ripening-related changes in the development of CI, and its management by melatonin. ‘Langra’ and ‘Gulab Jamun’ cultivar mango fruit was immersed in 100 μM of melatonin before storage for 28 days at 5°C with weekly transfers to shelf life at 25°C. CI symptom development was associated with compositional and enzymatic aspects of textural changes, cell membrane deterioration, and chemical energy status. Melatonin-treated ‘Langra’ fruit exhibited very low CI (5 vs. 21%) while ‘Gulab Jamun’ fruit exhibited higher CI (36 vs. 38%) during 28 days of storage at 5 ± 1°C. Higher chilling tolerance in melatonin-treated ‘Langra’ was associated with lower softening, ascribed to lower cell wall degrading exo- and endo-polygalacturonase, pectinesterase, and endo-1,4-β-D-glucanase. In addition, lower membrane deteriorating-phospholipase D and lipoxygenase activity in melatonin-treated ‘Langra’ corresponded to lower palmitic and stearic acids and higher oleic, linoleic, and linolenic acids accumulation, thus, higher unsaturated/saturated fatty acids ratio. Additionally, there was a higher intracellular energy supply with melatonin, represented by a higher adenylate energy charge (AEC) arising from higher ATP and ADP and lower AMP accumulation, related to higher H+-ATPase, Ca2+-ATPase, succinate dehydrogenase, and cytochrome c oxidase activities. This study for the first time provides evidence, suggesting that melatonin alleviation of CI is related to the preservation of membrane integrity, thereby protecting the intracellular energy supply, and preserving cell wall integrity via impeding cell wall degrading enzyme activities.
Estrogen Receptor and Claudin-6 Might Play Vital Roles for Long-Term Prognosis in Patients With Luminal A Breast Cancer Who Underwent Neoadjuvant Chemotherapy
Authors: Liu Yushi , Kang Ye , Li Jianyi , Zhang Yang , Jia Shi , Sun Qiang , Ma Yan , Zhang Jing , Wang Zhenrong , Cao Yanan , Shen Yang
Published: June 2022

Purpose

It is well-known that the pathological complete response (pCR) rate in patients with luminal A cancer (LAC) is lower than those of other subtypes of breast cancer. The phenotype of cancer often alters after neoadjuvant chemotherapy (NAC) which may be related to hypoxia, and the latter might induce the drift of the estrogen receptor (ER). The phenotype drift in local advanced LAC after NAC might influence the long-term prognosis.

Methods

The oxygen concentration of cancer tissues during NAC was recorded and analyzed (n = 43). The expression of ER and claudin-6 was detected in pre- and post-NAC specimens.

Results

NAC might induce the cycling intracanceral hypoxia, and the pattern was related to NAC response. The median follow-up time was 61 months. Most of the patients (67%) with stable or increased ER and claudin-6 expression exhibited perfect prognosis (DFS = 100%, 61 months). About 20% of patients with decreased claudin-6 would undergo the poor prognosis (DFS = 22.2%, 61 months). The contrasting prognosis (100% vs. 22.2%) had nothing to do with the response of NAC in the above patients. Only 13% patients had stable claudin-6 and decreased ER, whose prognosis might relate to the response of NAC.

Conclusion

NAC might induce cycling intracanceral hypoxia to promote the phenotype drift in local advanced LAC, and the changes in ER and claudin-6 after NAC would determine the long-term prognosis.
Sanguinarine Regulates Tumor-Associated Macrophages to Prevent Lung Cancer Angiogenesis Through the WNT/β-Catenin Pathway
Authors: Cui Yajing , Luo Yingbin , Qian Qiaohong , Tian Jianhui , Fang Zhihong , Wang Xi , Zeng Yaoying , Wu Jianchun , Li Yan
Published: June 2022

Tumor-associated macrophage (TAM)-mediated angiogenesis in the tumor microenvironment is a prerequisite for lung cancer growth and metastasis. Therefore, targeting TAMs, which block angiogenesis, is expected to be a breakthrough in controlling the growth and metastasis of lung cancer. In this study, we found that Sanguinarine (Sang) inhibits tumor growth and tumor angiogenesis of subcutaneously transplanted tumors in Lewis lung cancer mice. Furthermore, Sanguinarine inhibited the proliferation, migration, and lumen formation of HUVECs and the expression of CD31 and VEGF by regulating the polarization of M2 macrophages in vitro. However, the inhibitory effect of Sanguinarine on angiogenesis remained in vivo despite the clearance of macrophages using small molecule drugs. Further high-throughput sequencing suggested that WNT/β-Catenin signaling might represent the underlying mechanism of the beneficial effects of Sanguinarine. Finally, the β-Catenin activator SKL2001 antagonized the effect of Sanguinarine, indicating that Sanguinarine can regulate M2-mediated angiogenesis through the WNT/β-Catenin pathway. In conclusion, this study presents the first findings that Sanguinarine can function as a novel regulator of the WNT/β-Catenin pathway to modulate the M2 macrophage polarization and inhibit angiogenesis, which has potential application value in immunotherapy and antiangiogenic therapy for lung cancer.
Co-Treatment of Chloroquine and Trametinib Inhibits Melanoma Cell Proliferation and Decreases Immune Cell Infiltration
Authors: Degan Simone , May Brian L. , Jin Yingai J. , Hammouda Manel Ben , Sun Huiying , Zhang Guoqiang , Wang Yan , Erdmann Detlev , Warren Warren , Zhang Jennifer Y.
Published: June 2022

Autophagy is characterized as a cytoprotective process and inhibition of autophagy with medicinally active agents, such as chloroquine (CQ) is proposed as a prospective adjuvant therapy for cancer. Here, we examined the preclinical effects of CQ combined with the MEK inhibitor trametinib (TRA) on melanoma. We found that cotreatment of CQ and TRA markedly slowed melanoma growth induced in Tyr-CreER.BrafCa.Ptenfl/fl mice. Immunostaining showed that trametinib decreased Ki-67+ proliferating cells, and increased TUNEL+ apoptotic cells. The combo treatment induced a further decrease of Ki-67+ proliferating cells. Consistent with the in vivo findings, CQ and TRA inhibited melanoma cell proliferation in vitro, which was correlated by decreased cyclin D1 expression. In addition, we found that tissues treated with CQ and TRA had significantly decreased numbers of CD4+ and CD8+ T-lymphocytes and F4/80+ macrophages. Together, these results indicate that cotreatment of CQ and TRA decreases cancer cell proliferation, but also dampens immune cell infiltration. Further study is warranted to understand whether CQ-induced immune suppression inadvertently affects therapeutic benefits.
A Transcription Factor Signature Can Identify the CMS4 Subtype and Stratify the Prognostic Risk of Colorectal Cancer
Authors: Zhong Min-Er , Huang Ze-Ping , Wang Xun , Cai Du , Li Cheng-Hang , Gao Feng , Wu Xiao-Jian , Wang Wei
Published: June 2022

Background

Colorectal cancer (CRC) is a heterogeneous disease, and current classification systems are insufficient for stratifying patients with different risks. This study aims to develop a generalized, individualized prognostic consensus molecular subtype (CMS)-transcription factors (TFs)-based signature that can predict the prognosis of CRC.

Methods

We obtained differentially expressed TF signature and target genes between the CMS4 and other CMS subtypes of CRC from The Cancer Genome Atlas (TCGA) database. A multi-dimensional network inference integrative analysis was conducted to identify the master genes and establish a CMS4-TFs-based signature. For validation, an in-house clinical cohort (n = 351) and another independent public CRC cohort (n = 565) were applied. Gene set enrichment analysis (GSEA) and prediction of immune cell infiltration were performed to interpret the biological significance of the model.

Results

A CMS4-TFs-based signature termed TF-9 that includes nine TF master genes was developed. Patients in the TF-9 high-risk group have significantly worse survival, regardless of clinical characteristics. The TF-9 achieved the highest mean C-index (0.65) compared to all other signatures reported (0.51 to 0.57). Immune infiltration revealed that the microenvironment in the high-risk group was highly immune suppressed, as evidenced by the overexpression of TIM3, CD39, and CD40, suggesting that high-risk patients may not directly benefit from the immune checkpoint inhibitors.

Conclusions

The TF-9 signature allows a more precise categorization of patients with relevant clinical and biological implications, which may be a valuable tool for improving the tailoring of therapeutic interventions in CRC patients.
Injectable Hydrogel System for Camptothecin Initiated Nanocatalytic Tumor Therapy With High Performance
Authors: Wang Shuntao , Zhang Qi , Zeng Ning , Qi Pengyuan , Huang Chunyu , Huang Qinqin
Published: June 2022

Single photothermal therapy (PTT) has many limitations in tumor treatments. Multifunctional nanomaterials can cooperate with PTT to achieve profound tumor killing performance. Herein, we encapsulated chemotherapeutic drug camptothecin (CPT) and pyrite (FeS2) with dual enzyme activity (glutathione oxidase (GSH-OXD) and peroxidase (POD) activities) into an injectable hydrogel to form a CFH system, which can improve the level of intratumoral oxidative stress, and simultaneously realize FeS2-mediated PTT and nanozymes catalytic treatment. After laser irradiation, the hydrogel gradually heats up and softens under the photothermal agent FeS2. The CPT then released from CFH to tumor microenvironment (TME), thereby enhancing the H2O2 level. As a result, FeS2 can catalyze H2O2 to produce ·OH, and cooperate with high temperature to achieve high-efficiency tumor therapy. It is worth noting that FeS2 can also deplete excess glutathione (GSH) in the cellular level, further amplifying oxidative stress. Both in vivo and in vitro experiments show that our CFH exhibits good tumor-specific cytotoxicity. The CFH we developed provides new insights for tumor treatment.
A Novel Algorithm for Detecting Microsatellite Instability Based on Next-Generation Sequencing Data
Authors: Li Shijun , Wang Bo , Chang Miaomiao , Hou Rui , Tian Geng , Tong Ling
Published: June 2022

Objectives

Microsatellite instability (MSI) is the condition of genetic hypermutability caused by spontaneous acquisition or loss of nucleotides during the DNA replication. MSI has been discovered to be a useful immunotherapy biomarker clinically. The main DNA-based method for MSI detection is polymerase chain reaction (PCR) amplification and fragment length analysis, which are costly and laborious. Thus, we developed a novel method to detect MSI based on next-generation sequencing (NGS) data.

Methods

We chose six markers of MSI. After alignment and reads counting, a histogram was plotted showing the counts of different lengths for each marker. We then designed an algorithm to discover peaks in the generated histograms so that the peak numbers discovered in NGS data resembled that in PCR-based method.

Results

We selected nine samples as the training dataset, 101 samples for validation, and 68 samples as the test dataset from Chifeng Municipal Hospital, Inner Mongolia, China. The NGS-based method achieved 100% accuracy for the validation dataset and 98.53% accuracy for the test dataset, in which only one false positive was detected.

Conclusions

Accurate MSI judgments were achieved using NGS data, which could provide comparable MSI detection with the gold standard, PCR-based methods.
The Prevalence and Associated Risk Factors of Children With Reading Disabilities in a Multiethnic City: A Cross-Sectional Study
Authors: Feng Yanan , Liu Qi , Xie Xinyan , Jiang Qi , Zhu Kaiheng , Xiao Pei , Wu Xiaoqian , Zuo Pengxiang , Song Ranran
Published: June 2022

Numerous studies have been conducted to explore the risk factors for reading disabilities (RDs) among children. Based on these studies, factors such as gender, socioeconomic status, and the home literacy environment have been widely found to be associated with children who have RDs. However, children from a multiethnic city are seldom investigated. This study aimed to explore the prevalence of RDs and the potential environmental risk factors in Shihezi, Xinjiang, where people of multiple ethnicities, including Han and ethnic minority children, live and study together. A cross-sectional study was conducted in the city of Shihezi. A two-stage sampling strategy was applied to randomly select six primary schools in the city. In total, 6,539 students in grades two to six participated in this study. There were 6,065 valid questionnaires obtained for further analyses. We used the Dyslexia Checklist for Chinese Children and the Pupil Rating Scale to screen for the children with RDs. The χ2 test and multivariate logistic regression were employed to reveal the potential risk factors of RDs. The prevalence of children with RDs was 3.38% in Shihezi City and was significantly different between Han (3.28%) and Uighur (7.42%) children (P < 0.05). There was no significant difference in the prevalence of RDs between Han and Hui children. Among these children with RDs, the gender ratio of boys to girls was nearly 2:1. Multiple logistic regression analysis showed that gender (P < 0.01), learning habits (P < 0.01), and the home literacy environment (P < 0.01) were associated with RD. The results may be useful in the early identification and intervention of children with RDs, especially among ethnic minorities.
Ultrasound-Guided Modified Seldinger Placement of Tenckhoff Catheters in Pediatric Patients Undergoing Peritoneal Dialysis: Single Center Experience
Authors: Yu Yang , Xie Qing , Chen Yaxian , Hu Wanmei , Zhang Panpan , Huang Shi , Yang Fengjie , He Yonghua , Yi Yonghong , Zhou Jianhua , Zhang Yu
Published: June 2022

Minimally invasive peritoneal dialysis (PD) catheterization is increasingly common, and percutaneous PD catheters may be placed using a trocar or the Seldinger technique. There are few reports of pediatric percutaneous PD catheter insertion. We retrospectively compared the outcomes from percutaneous placement of Tenckhoff catheters using a modified Seldinger technique with catheter placement by open surgery. This single-center retrospective study compared 14 pediatric patients who received percutaneous PD catheter insertion using an ultrasound-guided modified Seldinger technique (August 2018–February 2021) with 10 patients who received open-surgical PD catheter insertion (2015–2018). Complications and catheter survival were evaluated. The overall technical success rate was 100%, but the Seldinger technique required less time (30 vs. 45 min) and smaller incisions (1.1 vs. 4.4 cm). The early complications in the Seldinger and control groups were bleeding (1 vs. 0), catheter dysfunction (1 vs. 1), abdominal pain (3 vs. 7), and exit leakage (0 vs. 1). In the Seldinger group, the median time from insertion to first use was 3 days, and the minimum follow-up was 6 months. Catheter survival at 6 months was 93% (Seldinger group) and 90% (open surgery group). The adoption of this technique at our institution led to a significant increase in the percentage of new pediatric dialysis patients commencing PD rather than hemodialysis. Collectively, the modified Seldinger technique described here was safe and feasible in pediatric patients. This approach is simpler and more rapid than open surgery, and reduces early complications and increases PD uptake.
Pediatric Emergency Cases in the First Year of the COVID-19 Pandemic in a Tertiary-Level Emergency Setting
Authors: Cozzi Giorgio , Molina Ruiz Idoya , Giudici Fabiola , Romano Sara , Grigoletto Veronica , Barbi Egidio , Amaddeo Alessandro
Published: June 2022

Aim

Emergency cases are uncommon events in the pediatric emergency setting. This study aimed to evaluate the effect of the Coronavirus disease 2019 (COVID-19) pandemic by describing the number and type of pediatric emergency cases that arrived at the pediatric emergency department (PED) of a tertiary-level children’s hospital in Italy.

Methods

We performed a retrospective study, collecting the main features of pediatric emergency patients who arrived during the first year of the COVID-19 pandemic (March 2020–February 2021) compared to the pre-pandemic period (March 2016–February 2020).

Results

During the study period, 112,168 patients were visited at the PED, and 237 (0.21%) were emergency cases, median age of 4 years (IQR: 1–12). In the first year of the pandemic, 42 children were coded as emergency cases compared to 195 (49/year) during the pre-pandemic period. The proportion of emergency cases was stable (0.27% during the COVID-19 period versus 0.20% during the pre-COVID-19 period, p = 0.19). No differences were found regarding the age, gender, hour of arrival, and outcome of patients. We found a significant decrease in the proportion of emergency cases related to respiratory diseases (9/42, 21.4% during the COVID-19 period versus 83/195 during the pre-COVID-19 period (42.6%), p = 0.01).

Conclusion

In conclusion, our data suggest that the pandemic had a more significant impact on respiratory emergency cases than on pediatric emergencies in general.
Disentangling Generative Factors of Physical Fields Using Variational Autoencoders
Authors: Jacobsen Christian , Duraisamy Karthik
Published: June 2022

The ability to extract generative parameters from high-dimensional fields of data in an unsupervised manner is a highly desirable yet unrealized goal in computational physics. This work explores the use of variational autoencoders for non-linear dimension reduction with the specific aim ofdisentanglingthe low-dimensional latent variables to identify independent physical parameters that generated the data. A disentangled decomposition is interpretable, and can be transferred to a variety of tasks including generative modeling, design optimization, and probabilistic reduced order modelling. A major emphasis of this work is to characterize disentanglement using VAEs while minimally modifying the classic VAE loss function (i.e., the Evidence Lower Bound) to maintain high reconstruction accuracy. The loss landscape is characterized by over-regularized local minima which surround desirable solutions. We illustrate comparisons between disentangled and entangled representations by juxtaposing learned latent distributions and the true generative factors in a model porous flow problem. Hierarchical priors are shown to facilitate the learning of disentangled representations. The regularization loss is unaffected by latent rotation when training with rotationally-invariant priors, and thus learning non-rotationally-invariant priors aids in capturing the properties of generative factors, improving disentanglement. Finally, it is shown that semi-supervised learning - accomplished by labeling a small number of samples (O(1%))–results in accurate disentangled latent representations that can be consistently learned.
Diode-Pumped 50 Hz–10 J Nano-Second Nd:YAG Laser
Authors: Jiang Xinying , Xiao Kaibo , Yan Xiongwei , Wang Zhenguo , Jiang Xuejun , Xue Qiao , Wu Wenlong , Chen Ji , Zhang Chuanchao , Zheng Jiangang , Peng Zhitao , Zheng Kuixing , Li Ping , Hu Dongxia , Zhu Qihua , Zheng Wanguo
Published: June 2022

In this letter, we report a diode-pumped nano-second laser with the output energy 10 J, the repetition rate 50 Hz, and the average power 500 W. The main amplifier was made up of eight amplify modules. Each amplify module was pumped by an 808 nm laser diode and cooled by water from the back end of the Nd:YAG slab. To our knowledge, this represents the highest pulse repetition rate for the 10 J class nano-second single-aperture Nd:YAG laser. The beam quality was controlled by means of mechanical design and adjustment and compensation by a home-made deforming mirror. The beam quality was controlled well with the beam quality of the laser 2.61DL.
A Novel Method to Determine the Cause of Left Internal Mammary Artery Instant Non-Patency Based on Transit Time Flow Measurement
Authors: Mao Boyan , Feng Yue , Duan Mengyao , Dong Yihang , Li Gaoyang , Li Bao , Liu Jincheng , Guo Yuting , Wei Minghui , Zhao Zhou , Liu Youjun
Published: June 2022

Objective: After coronary artery bypass grafting (CABG) surgery, the main causes of poor instant patency of left internal mammary arteries (LIMAs) are competitive flow and anastomotic stenosis, but how to determine the cause of LIMA non-patency without interfering with the native coronary artery is still a difficult problem to be solved urgently.

Methods: In this study, a 0D-3D coupled multiscaled CABG model of anastomotic stenosis and competitive flow was constructed. After calculation, the flow waveform of the LIMA was extracted, and the waveform shape, common clinical parameters (average flow, PI, and DF), and graft flow FFT ratio results (F0/H1 and F0/H2) were analyzed.

Results: For LIMA, these three common clinical parameters did not differ significantly between the anastomotic stenosis group and competitive flow group. However, the waveform shape and FFT ratio (especially F0/H2) of the competitive flow group were significantly different from those of the anastomotic stenosis group. When the cause was competitive flow, there was systolic backflow, and F0/H2 was too high (>14.89). When the cause was anastomotic stenosis, the waveform maintained a bimodal state and F0/H2 was in a normal state (about 1.17).

Conclusion: When poor instant patency of the LIMA is found after CABG, the causes can be determined by graft flow waveform shape and F0/H2.