bluuebunny/crossref_metadata_2025 huggingface dataset:
Revolution of CAR Engineering For Next-Generation Immunotherapy In Solid Tumors
Authors: Yu Tao , Yu Shao-kun , Xiang Yan , Lu Kai-Hua , Sun Ming
Published: July 2022

Chimeric antigen receptor (CAR)-T cells have enormous potentials for clinical therapies. The CAR-T therapy has been approved for treating hematological malignancies. However, their application is limited in solid tumors owing to antigen loss and mutation, physical barriers, and an immunosuppressive tumor microenvironment. To overcome the challenges of CAR-T, increasing efforts are put into developing CAR-T to expand its applied ranges. Varied receptors are utilized for recognizing tumor-associated antigens and relieving immunosuppression. Emerging co-stimulatory signaling is employed for CAR-T activation. Furthermore, other immune cells such as NK cells and macrophages have manifested potential for delivering CAR. Hence, we collected and summarized the last advancements of CAR engineering from three aspects, namely, the ectodomains, endogenous domains, and immune cells, aiming to inspire the design of next-generation adoptive immunotherapy for treating solid tumors.
Butenolide Insecticide Flupyradifurone Affects Honey Bee Worker Antiviral Immunity and Survival
Authors: Harwood Gyan P. , Prayugo Vincent , Dolezal Adam G.
Published: July 2022

Honey bees face many environmental stressors, including exposure to pesticides and pathogens. A novel butenolide pesticide, flupyradifurone, was recently introduced to the US and shown to have a bee-friendly toxicity profile. Like the much-scrutinized neonicotinoids that preceded it, flupyradifurone targets the insect nervous system. Some neonicotinoids have been shown to interfere with antiviral immunity, which raised the concern that similar effects may be observed with flupyradifurone. In this study, we investigated how flupyradifurone and a neonicotinoid, clothianidin, affect the ability of honey bee workers to combat an infection of Israeli acute paralysis virus (IAPV). We exposed workers to field-realistic doses of the pesticides either with or without co-exposure with the virus, and then tracked survival and changes in viral titers. We repeated the experiment in the spring and fall to look for any seasonal effects. We found that flupyradifurone caused elevated mortality in the fall, but it did not lead to increased virus-induced mortality. Flupyradifurone also appeared to affect virus clearance, as bees co-exposed to the pesticide and virus tended to have higher viral titers after 48 hours than those exposed to the virus alone. Clothianidin had no effect on viral titers, and it actually appeared to increase resistance to viral infection in spring bees.
Long-Term Variability of the East Sea Intermediate Water Thickness: Regime Shift of Intermediate Layer in the Mid-1990s
Authors: Park JongJin
Published: July 2022

The shipboard measurements over approximately 55 years in the southwestern part of the East Sea (Sea of Japan) demonstrate a remarkable basin-wide, interannual-interdecadal variability in the temperature-based thickness of the East Sea Intermediate Water (ESIW) whose temporal variability shows strong correlation with the density-based thickness (r = 0.97). Relevant to the long-term variability of the ESIW thickness, clear changes in horizonal and vertical features have been observed at the intermediate layer in the mid-1990s, such as 1) increases in vertical temperature gradient in the thermocline by shoaling of 2°C–5°C isotherms, 2) relatively high correlations among isotherms in the interdecadal timescale, 3) appearance of zonal phase difference in the ESIW thickness variability after the mid-1990s, and 4) correlation phase change between the Arctic Oscillation Index and the ESIW thickness. The ESIW thickness could be smaller when its formation is weaker and when the formation of deep-water mass below it becomes stronger. Based on the features observed, we hypothesized on the regime shift concerning the East Sea meridional overturning circulation; before the mid-1990s, active deep-water formation mainly controlled the ESIW layer variability, but after the mid-1990s, the ESIW formation rate predominantly affected its own thickness variability.
Contrasting Diversity and Composition of Human Colostrum Microbiota in a Maternal Cohort With Different Ethnic Origins but Shared Physical Geography (Island Scale)
Authors: Xie Wanying , Zhang Huimin , Ni Yongqing , Peng Yunhua
Published: July 2022

Colostrum represents an important source for the transfer of important commensal bacteria from mother to newborn and has a strong impact on the newborn’s health after birth. However, the composition of the colostrum microbiome is highly heterogeneous due to geographic factors and ethnicity (maternal, cultural, and subsistence factors). By analyzing the colostrum 16S rRNA gene full-length sequencing dataset in 97 healthy mothers (60 from Han, 37 from Li) from the Hainan island of China, we showed that the ethnic differences of the colostrum microbiome in a maternal cohort with different ethnic origins shared physical geography. Results indicated that the richness of microbial community in colostrum of Han women was higher than that of Li women, but there was no significant difference in Shannon index and invsimpson index between the two groups. Visualization analysis based on the distance showed an obvious ethnicity-associated structural segregation of colostrum microbiota. The relative abundance of Firmicutes was higher in the microbiota of the Han group than in Li’s, while Proteobacteria was on the contrary. At the genus level, the most dominant members of the Han and Li ethnic groups were Acinetobacter and Cupriavidus, two common environmental bacteria, respectively, although skin-derived Staphylococcus and Streptococcus were still subdominant taxa. Cupriavidus lacunae was the most dominant species in the Li group, accounting for 26.10% of the total bacterial community, but only 3.43% for the Han group with the most dominant Staphylococcus petrasii (25.54%), indicating that human colostrum microbiome was more susceptible to local living environmental factors. Hence, the ethnic origin of individuals may be an important factor to consider in human milk microbiome research and its potential clinical significance during the perinatal period in ethnic-diverse societies, even within a small geographic scale.
Reduced HGF/MET Signaling May Contribute to the Synaptic Pathology in an Alzheimer's Disease Mouse Model
Authors: Wei Jing , Ma Xiaokuang , Nehme Antoine , Cui Yuehua , Zhang Le , Qiu Shenfeng
Published: July 2022

Alzheimer's disease (AD) is a neurodegenerative disorder strongly associates with aging. While amyloid plagues and neurofibrillary tangles are pathological hallmarks of AD, recent evidence suggests synaptic dysfunction and physical loss may be the key mechanisms that determine the clinical syndrome and dementia onset. Currently, no effective therapy prevents neuropathological changes and cognitive decline. Neurotrophic factors and their receptors represent novel therapeutic targets to treat AD and dementia. Recent clinical literature revealed that MET receptor tyrosine kinase protein is reduced in AD patient's brain. Activation of MET by its ligand hepatocyte growth factor (HGF) initiates pleiotropic signaling in the developing brain that promotes neurogenesis, survival, synaptogenesis, and plasticity. We hypothesize that if reduced MET signaling plays a role in AD pathogenesis, this might be reflected in the AD mouse models and as such provides opportunities for mechanistic studies on the role of HGF/MET in AD. Examining the 5XFAD mouse model revealed that MET protein exhibits age-dependent progressive reduction prior to overt neuronal pathology, which cannot be explained by indiscriminate loss of total synaptic proteins. In addition, genetic ablation of MET protein in cortical excitatory neurons exacerbates amyloid-related neuropathology in 5XFAD mice. We further found that HGF enhances prefrontal layer 5 neuron synaptic plasticity measured by long-term potentiation (LTP). However, the degree of LTP enhancement is significantly reduced in 5XFAD mice brain slices. Taken together, our study revealed that early reduction of HGF/MET signaling may contribute to the synaptic pathology observed in AD.
Zinc Phthalocyanine Tetrasulfonate-Loaded Ag@mSiO2 Nanoparticles for Active Targeted Photodynamic Therapy of Colorectal Cancer
Authors: Montaseri Hanieh , Simelane Nokuphila Winifred Nompumelelo , Abrahamse Heidi
Published: July 2022

Colorectal cancer has high morbidity and mortality rate, with a high level of metastasis and recurrence due to the poor therapeutic effects. Photodynamic therapy (PDT) as an emerging clinical modality for cancer treatment provides remarkable advantages over existing treatments by generating reactive oxygen species (ROS) through light irradiating photosensitizers (PSs) in the presence of oxygen. PDT can induce immunity against recurrence and destruction of metastases. The application of nanoparticles (NPs) in targeted cancer therapy is coming to light to circumvent the limitations associated with low physiological solubility and lack of selectivity of the PS towards tumor sites. In this in vitro study, we proved the added value of NP systems on PS efficacy and a tumor-targeting ligand. Using core/shell Ag@mSiO2 NPs loaded with ZnPcS4 PS and folic acid (FA), stronger cellular localization in the human colorectal cancer cell line (Caco-2) was observed compared to the passive NC and free PS. Additionally, light-induced photodynamic activation of the ZnPcS4/Ag@mSiO2-FA nanoconjugate (NC) elicited a strong cytotoxicity effect mediated by post-PDT. The results also revealed that the active NC was able to decrease the cell viability remarkably to 38.0% ± 4.2 *** compared to the passive NC (67.0% ± 7.4*) under 0.125 µM ZnPcS4 (IC50). More importantly, the actively targeted NC-induced apoptosis where cell cycle analysis elaborated on cell death through the G0 phase, indicating the final NC’s efficacy 20 hr post-PDT treatment.
The Association Between Different Types of Dietary Carbohydrates and Colorectal Cancer: A Case-Control Study
Authors: Jonoush Mona , Fathi Soroor , Hassanpour Ardekanizadeh Naeemeh , Khalatbari Mohseni Golsa , Majidi Nazanin , Keshavarz Seyed Ali , Shekari Soheila , Nemat Gorgani Shiva , Torki Saheb Abbas , Sotoudeh Mahtab , Habibi Fatemeh , Gholamalizadeh Maryam , Alizadeh Atiyeh , Doaei Saeid
Published: July 2022

Background

Several factors such as genetics and dietary intake are involved in the development of colorectal cancer (CRC). Higher intake of dietary carbohydrates may be associated with an increased risk of CRC. This study aimed to investigate the association between different types of dietary carbohydrates and CRC.

Methods

This hospital-based case–control study was carried out from June 2020 to May 2021 on 480 randomly selected participants including 160 CRC patients and 320 healthy controls aged 35–70 years in Firoozgar hospital, Tehran, Iran. Dietary intake was assessed using Food Frequency Questionnaire (FFQ). Nutritionist IV software was used to determine the intake of calorie and various forms of dietary carbohydrates including total carbohydrate, simple sugar, glucose, fructose, galactose, sucrose, lactose, and maltose.

Results

The average daily intake of calorie, carbohydrates, sugar, glucose, fructose, sucrose, and maltose were significantly higher among CRC cases compared to the controls (All P < 0.05). The logistic regression found significant associations between CRC with dietary intake of carbohydrates (OR = 1.009, CI 95%: 1.003–1.01, P = 0.002), sugar (OR = 1.02, CI 95%: 1.01–1.03, P < 0.001), glucose (OR = 1.06, CI 95%: 1.01–1.11, P = 0.009), fructose (OR = 1.31, CI 95%: 1.19–1.43, P < 0.001), sucrose (OR = 1.19, CI 95%: 1.12.−1.25, P < 0.001), maltose (OR = 9.03, CI 95%: 3.93–20.78, P < 0.001), galactose (OR = 1.31, CI 95%: 1.07–1.6, P = 0.008), and lactose (OR = 1.009, CI 95%: 1.01–1.18, P = 0.02). This association remained significant after adjustment for sex and age (except for galactose and lactose), and additional adjustment for sleep, tobacco, and alcohol level, and further adjustment for calorie intake and body mass index (BMI) (except for glucose).

Conclusions

A positive association was found between CRC and dietary intake of carbohydrates, sugar, fructose, sucrose, and maltose. Following a low-carbohydrate, low-sugar diet may help prevent CRC. Future longitudinal studies are warranted to confirm these findings.
Case Report: Can Targeted Intraoperative Radiotherapy in Patients With Breast Cancer and Pacemakers be the New Standard of Care?
Authors: Bhimani Fardeen , Johnson Kelly , Brodin N. Patrik , Tomé Wolfgang A. , Fox Jana , Mehta Keyur , McEvoy Maureen , Feldman Sheldon
Published: July 2022

Background

Partial breast irradiation with Intra-operative radiotherapy (IORT) has become a popular management option as opposed to whole breast radiation using external beam radiotherapy for breast cancer patients. While previous studies have highlighted the use of IORT in breast cancer patients, there is a scarcity of literature on the use of IORT in those who also have ipsilateral pacemakers. Thus, the aim of our case report is to highlight the applicability of IORT in breast cancer patients who also have a pacemaker.

Case Reports

Two female patients with an implanted dual-chamber pacemaker presented with a diagnosis of left-sided invasive ductal carcinoma on mammogram. Mammography of the left breast revealed a 10 mm and 7 mm spiculated mass, respectively, further confirmed with an ultrasound-guided core biopsy that was conclusive of clinical Stage I T1 N0 grade 2, ER +, PR + Her2 – invasive ductal carcinoma. They met our eligibility criteria for IORT, which is being performed as a registry trial. These patients underwent a wide excision lumpectomy along with IORT.

Conclusion

Our findings underscore the successful use of targeted IORT for breast-conserving surgery in a patient with invasive ductal carcinoma and pacemaker, hence eliminating the necessity for relocating pacemaker surgeries in these patients. Furthermore, no device failure or malfunction for the pacemaker was recorded before, during, or after the surgery, demonstrating the safety of using IORT in patients with preinstalled pacemaker despite a lack of evidence on safe radiation dosage or manufacturer guidelines. Nonetheless, the effects of IORT on pacemaker < 10 cm were not studied in our patients and further clinical studies are recommended to reinforce the applicability and safe distance of IORT in breast cancer patients with pacemaker.
Endoscopic Resection Versus Surgery in the Treatment of Early Gastric Cancer: A Systematic Review and Meta-Analysis
Authors: Bestetti Alexandre Moraes , de Moura Diogo Turiani Hourneaux , Proença Igor Mendonça , Junior Epifanio Silvino do Monte , Ribeiro Igor Braga , Sasso João Guilherme Ribeiro Jordão , Kum Angelo So Taa , Sánchez-Luna Sergio A. , Marques Bernardo Wanderley , de Moura Eduardo Guimarães Hourneaux
Published: July 2022

Background and Aim

Endoscopic resection (ER) is the preferred approach to treat early gastric cancer (EGC) in patients without suspected lymph node involvement and that meet the criteria for ER. Surgery is a more aggressive treatment, but it may be associated with less recurrence and the need for reintervention. Previous meta-analyses comparing ER with surgery for EGC did not incorporate the most recent studies, making accurate conclusions not possible.

Methods

This systematic review and meta-analysis aimed to examine complete resection, length of hospital stay (LOHS), adverse events (AEs), serious AEs, recurrence, 5-year overall survival (OS), and 5-year cancer-specific survival (CSS) in patients with EGC.

Results

A total of 29 cohorts studies involving 20559 patients were included. The ER (n = 7709) group was associated with a lower incidence of AEs (RD = -0.07, 95%CI = -0.1, -0.04, p < 0.0001) and shorter LOHS (95% CI -5.89, -5.32; p < 0,00001) compared to surgery (n = 12850). However, ER was associated with lower complete resection rates (RD = -0.1, 95%CI = -0.15, -0.06; p < 0.00001) and higher rates of recurrence (RD = 0.07, 95%CI = 0.06; p < 0.00001). There were no significant differences between surgery and ER in 5-year OS (RD = -0.01, 95%CI = -0.04, 0.02; p = 0.38), 5-year CSS (RD = 0.01, 95%CI = 0.00, 0.02; p < 0.17), and incidence of serious AEs (RD = -0.03, 95%CI = -0.08, 0.01; p = 0.13).

Conclusions

ER and surgery are safe and effective treatments for EGC. ER provides lower rates of AEs and shorter LOHS compared to surgery. Although ER is associated with lower complete resection rates and a higher risk of recurrence, the OS and CSS were similar between both approaches.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021255328.
Impact of the COVID-19 Pandemic on Patient- and Family-Centered Care and on the Mental Health of Health Care Workers, Patients, and Families
Authors: Lessa Alessandra Rodrigues Dias , Bitercourt Victória Noremberg , Crestani Francielly , Andrade Gabriela Rupp Hanzen , Costa Caroline Abud Drumond , Garcia Pedro Celiny Ramos
Published: July 2022

During the COVID-19 pandemic, hospitals around the world were forced to reorganize their processes in an attempt to contain the spread of the virus while still providing adequate care to patients. In the Pediatric Intensive Care Unit (PICU) setting, changes in family visitation protocols and restrictions on parent chaperones during hospitalization, as well as other changes, interfered with care. Based on a narrative review of the literature, supported by the authors' observations in practice, we aimed to describe the impact of the pandemic on patient and family-centered care (PFCC) in the PICU environment, especially regarding the presence of family members, family support, and communication with patients and their families, as well as the effects of changes in these practices on the mental health of those involved. In this context, several strategies were used to sustain PFCC, and, despite many challenges, attempts were made to achieve the bare-minimum goals of humanized care for patients, families, and providers alike.
Mechanistic Research for the Student or Educator (Part II of II)
Authors: Leak Rehana K. , Schreiber James B.
Published: July 2022

This two-part series describes how to test hypotheses on molecular mechanisms that underlie biological phenomena, using preclinical drug testing as a simplified example. While pursuing drug testing in preclinical research, students will need to understand the limitations of descriptive as well as mechanistic studies. The former does not identify any causal links between two or more variables; it identifies the presence or absence of correlations. Parts I and II of this educational series encourage the student to 1) ensure the sensitivity and specificity of their measurements, 2) establish or optimize an appropriate disease model, 3) find pharmaceutical drug doses/concentrations that interfere with experimental disease processes, 4) leverage the literature and exploratory datasets to craft a mechanism-oriented hypothesis on drug binding and downstream effects, 5) and design a full-factorial experiment to test the hypothesis after sketching potential outcomes and imagining their interpretations. These creative goals facilitate the choice of the appropriate positive and negative controls to avoid false data interpretations. Here, Part II describes in detail how to test for a causal link between drug-induced activation of biological targets and therapeutic outcomes. Upon completion of this two-part series, the new student will have some of the tools in hand to design mechanistic studies, interpret the outcomes of their research, and avoid technical and theoretical pitfalls, which can otherwise decelerate scientific progress and squander human and financial resources.
Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification
Authors: Long Yingxin , Li Zunjiang , Huang Chunxia , Lu Zhongyu , Qiu Kuncheng , He Meixing , Fang Zhijian , Ding Banghan , Yuan Xiaohong , Zhu Wei
Published: July 2022

Smilax glabra Roxb (SGR) has been widely applied alone or in combination with other Chinese herbs in heart failure (HF), but its mechanism and protective effect have not been investigated. We aimed to explore the mechanism and protective effect of SGR on the treatment of HF. Network pharmacology analysis predicted that SGR was involved in the regulation of cell proliferation, oxidation–reduction process, apoptotic process, ERK1 and ERK2 cascade, MAPK cascade, etc. Its mechanism was mainly involved in the MAPK signaling pathway, calcium signaling pathway, cardiac muscle contraction, etc. Subsequently, SGR was proved to improve cellular viability, restore cellular morphology, suppress cellular and mitochondrial ROS production, improve H2O2-induced lysosome inhibition, attenuate mitochondrial dysfunction, and protect mitochondrial respiratory and energy metabolism in H9c2 cells. SGR activated the p38MAPK pathway by decreasing the mRNA expression of AKT, PP2A, NF-KB, PP2A, RAC1, and CDC42 and increasing the mRNA expression of Jun, IKK, and Sirt1. SGR also decreased the protein expression of ERK1, ERK2, JNK, Bax, and Caspase3 and increased the protein expression of p38MAPK and Bcl-2. In addition, Istidina at the highest degree was identified in SGR via the UHPLCLTQ-Orbitrap-MSn method, and it was suggested as anti-heart failure agents by targeting SRC with molecular docking analysis. In conclusion, SGR has a protective effect on HF through cellular and mitochondrial protection via multi-compounds and multi-targets, and its mechanism is involved in activating the p38 MAPK pathway. Istidina may be possible anti-HF agents by targeting SRC.
Evaluation of LiangXue JieDu Therapy in Combination With Western Medicine for Acute-On-Chronic Liver Failure: A Systematic Review and meta-Analysis
Authors: Shi Ke , Zhang Qun , Hou Jie , Zhang Yi , Bi Yufei , Wang Xianbo
Published: July 2022

Objectives: To assess the efficacy of LiangXue JieDu (LXJD) therapy in combination with Western medicine (WM) for acute-on-chronic liver failure (ACLF).

Methods: Articles on randomized controlled trials of LXJD therapy for ACLF were obtained from PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, VIP, Wanfang, and China Biology Medicine databases, with the search range from database inception to March 2022. We evaluated the quality of data from these articles using the Cochrane risk-of-bias tool. Evaluation indicators were total effective rate, mortality rate, complications, liver and coagulation function, and Traditional Chinese medicine (TCM) syndrome score. We then calculated the risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables with a 95% confidence interval (CI).

Results: The meta-analysis included 18 studies with moderate quality and totaling 1,609 patients. Compared with WM alone, LXJD therapy plus WM improved total effective rate [RR = 1.34, 95% CI: (1.24, 1.45)], while reducing mortality rate [RR = 0.54, 95% CI: (0.42, 0.70)] and complications [RR = 0.43, 95% CI: (0.26, 0.71)]. The combined treatment also improved prothrombin activity [MD = 1.30, 95% CI: (1.02, 1.59)], prothrombin time [MD = −0.90, 95% CI: (−1.40, −0.39)], international normalized ratio [MD = −0.59, 95% CI: (−0.93, −0.25)], alanine aminotransferase [MD = −0.92, 95% CI: (−1.30, −0.55)], aspartate aminotransferase [MD = −0.57, 95% CI: (−0.93, −0.21)], total bilirubin [MD = −1.07, 95% CI: (−1.38, −0.76)], and TCM syndrome score [MD = −1.70; 95% CI: (−2.03, −1.37)].

Conclusions: This study suggests that LXJD therapy plus WM can significantly improves ACLF clinical symptoms and short-term outcomes. However, more high-quality trials are required to confirm the efficacy of LXJD therapy.
Number 2 Feibi Recipe Ameliorates Pulmonary Fibrosis by Inducing Autophagy Through the GSK-3β/mTOR Pathway
Authors: Liu Haoge , Pang Qinglu , Cao Fang , Liu Zhaoheng , Wei Wan , Li Zhipeng , Long Qi , Jiao Yang
Published: July 2022

Number 2 Feibi Recipe (N2FBR) is a traditional Chinese medicine formula for treating idiopathic pulmonary fibrosis. N2FBR inhibits H2O2-mediated oxidative stress damage in alveolar epithelial cells by increasing autophagy, as we previously demonstrated. However, it is unknown if similar mechanisms occur in vivo. We established a pulmonary fibrosis model by instilling bleomycin (BLM) from the airway to examine the effects of N2FBR on pulmonary fibrosis and investigate its probable mechanism in this work. We discovered that N2FBR treatment effectively alleviated interstitial fibrosis as well as collagen deposition, primarily in upregulating SOD, GSH-Px, T-AOC and downregulating MDA content. N2FBR also increased the expression of LC3B, Beclin-1, LAMP1, TFEB and downregulated the expression of p62, legumain. N2FBR treatment boosted the production of autophagosomes, according to the results of the TEM observation. Furthermore, we explored that N2FBR exerted its anti-oxidative stress and pro-autophagy effects via GSK-3β/mTOR signalling pathway. Therefore, these results provide further evidence for the protective effect of N2FBR in pulmonary fibrosis. Our findings could have ramifications for the development of antifibrosis therapies.
The Antioxidant N-Acetyl-L-Cysteine Restores the Behavioral Deficits in a Neurodevelopmental Model of Schizophrenia Through a Mechanism That Involves Nitric Oxide
Authors: Lopes-Rocha Ana , Bezerra Thiago Ohno , Zanotto Roberta , Lages Nascimento Inda , Rodrigues Angela , Salum Cristiane
Published: July 2022

The disruption of neurodevelopment is a hypothesis for the emergence of schizophrenia. Some evidence supports the hypothesis that a redox imbalance could account for the developmental impairments associated with schizophrenia. Additionally, there is a deficit in glutathione (GSH), a main antioxidant, in this disorder. The injection of metilazoximetanol acetate (MAM) on the 17th day of gestation in Wistar rats recapitulates the neurodevelopmental and oxidative stress hypothesis of schizophrenia. The offspring of rats exposed to MAM treatment present in early adulthood behavioral and neurochemical deficits consistent with those seen in schizophrenia. The present study investigated if the acute and chronic (250 mg/kg) treatment during adulthood with N-acetyl-L-cysteine (NAC), a GSH precursor, can revert the behavioral deficits [hyperlocomotion, prepulse inhibition (PPI), and social interaction (SI)] in MAM rats and if the NAC-chronic-effects could be canceled by L-arginine (250 mg/kg, i.p, for 5 days), nitric oxide precursor. Analyses of markers involved in the inflammatory response, such as astrocytes (glial fibrillary acid protein, GFAP) and microglia (binding adapter molecule 1, Iba1), and parvalbumin (PV) positive GABAergic, were conducted in the prefrontal cortex [PFC, medial orbital cortex (MO) and prelimbic cortex (PrL)] and dorsal and ventral hippocampus [CA1, CA2, CA3, and dentate gyrus (DG)] in rats under chronic treatment with NAC. MAM rats showed decreased time of SI and increased locomotion, and both acute and chronic NAC treatments were able to recover these behavioral deficits. L-arginine blocked NAC behavioral effects. MAM rats presented increases in GFAP density at PFC and Iba1 at PFC and CA1. NAC increased the density of Iba1 cells at PFC and of PV cells at MO and CA1 of the ventral hippocampus. The results indicate that NAC recovered the behavioral deficits observed in MAM rats through a mechanism involving nitric oxide. Our data suggest an ongoing inflammatory process in MAM rats and support a potential antipsychotic effect of NAC.
Treatment of Liver Fibrosis: A 20-Year Bibliometric and Knowledge-Map Analysis
Authors: Dai Yun-Kai , Zhao Zhi-Min , Liu Chenghai
Published: July 2022

Objectives: To analyze the research hotspots, evolution, and trends of the treatment of liver fibrosis in the recent 20 years, bibliometric and knowledge-map analysis were used.

Methods: Publications associated with the treatment of liver fibrosis were retrieved from the Web of Science Core Collection on 16 April 2022. CiteSpace 5.8.R3 and VOSviewer 1.6.18 were calculated to perform bibliometric and knowledge-map analysis.

Results: A total of 72,686 authors from 200 institutions in 134 countries/regions published 15,237 studies in different academic journals. United States was the most productive country, and Shanghai Jiao Tong University was the most published institution. Trauner Michael had the most published articles, whereas Scott L. Friedman was the most frequently co-cited author. Moreover, there was frequent inter-institution cooperation between countries in the years 2015 and after, but the before years showed rare inter-institution cooperation. The journal HEPATOLOGY was both the most published publication and the most frequently co-cited one in this field. Screened keywords, such as virus infection, inflammation, oxidative stress, activation of hepatic stellate cell (HSC), and hepatocellular apoptosis, could be both therapeutic targets and pathological mechanisms in terms of liver fibrosis. Furthermore, long-term suppression of hepatitis B virus replication and the activation of HSC were the latest hotspots and topics related to the treatment of liver fibrosis. Besides, the treatments of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis were also involved in the treatment of liver fibrosis, which were both emerging topics and rapidly developing hot fields.

Conclusion: This bibliometric analysis conducted a full overview of the treatment of liver fibrosis, which provided important clues and ideas for scholars focusing on this field. Not only that, the field is still in a stage of rapid development and will continue to be a research hotspot in the future.
Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals
Authors: Kang Liang , Zhang Huaqing , Jia Chongyu , Zhang Renjie , Shen Cailiang
Published: July 2022

Low back pain is a major cause of disability worldwide that declines the quality of life; it poses a substantial economic burden for the patient and society. Intervertebral disc (IVD) degeneration (IDD) is the main cause of low back pain, and it is also the pathological basis of several spinal degenerative diseases, such as intervertebral disc herniation and spinal stenosis. The current clinical drug treatment of IDD focuses on the symptoms and not their pathogenesis, which results in frequent recurrence and gradual aggravation. Moreover, the side effects associated with the long-term use of these drugs further limit their use. The pathological mechanism of IDD is complex, and oxidative stress and inflammation play an important role in promoting IDD. They induce the destruction of the extracellular matrix in IVD and reduce the number of living cells and functional cells, thereby destroying the function of IVD and promoting the occurrence and development of IDD. Phytochemicals from fruits, vegetables, grains, and other herbs play a protective role in the treatment of IDD as they have anti-inflammatory and antioxidant properties. This article reviews the protective effects of phytochemicals on IDD and their regulatory effects on different molecular pathways related to the pathogenesis of IDD. Moreover, the therapeutic limitations and future prospects of IDD treatment have also been reviewed. Phytochemicals are promising candidates for further development and research on IDD treatment.
An Inexpensive Open-Source Chamber for Controlled Hypoxia/Hyperoxia Exposure
Authors: Hillman Tyler C. , Idnani Ryan , Wilson Christopher G.
Published: July 2022

Understanding hypoxia/hyperoxia exposure requires either a high-altitude research facility or a chamber in which gas concentrations are precisely and reproducibly controlled. Hypoxia-induced conditions such as hypoxic-ischemic encephalopathy (HIE), obstructive or central apneas, and ischemic stroke present unique challenges for the development of models with acute or chronic hypoxia exposure. Many murine models exist to study these conditions; however, there are a variety of different hypoxia exposure protocols used across laboratories. Experimental equipment for hypoxia exposure typically includes flow regulators, nitrogen concentrators, and premix oxygen/nitrogen tanks. Commercial hypoxia/hyperoxia chambers with environmental monitoring are incredibly expensive and require proprietary software with subscription fees or highly expensive software licenses. Limitations exist in these systems as most are single animal systems and not designed for extended or intermittent hypoxia exposure. We have developed a simple hypoxia chamber with off-the-shelf components, and controlled by open-source software for continuous data acquisition of oxygen levels and other environmental factors (temperature, humidity, pressure, light, sound, etc.). Our chamber can accommodate up to two mouse cages and one rat cage at any oxygen level needed, when using a nitrogen concentrator or premixed oxygen/nitrogen tank with a flow regulator, but is also scalable. Our system uses a Python-based script to save data in a text file using modules from the sensor vendor. We utilized Python or R scripts for data analysis, and we have provided examples of data analysis scripts and acquired data for extended exposure periods (≤7 days). By using FLOS (Free-Libre and open-source) software and hardware, we have developed a low-cost and customizable system that can be used for a variety of exposure protocols. This hypoxia/hyperoxia exposure chamber allows for reproducible and transparent data acquisition and increased consistency with a high degree of customization for each experimenter’s needs.
The Function of FoxK Transcription Factors in Diseases
Authors: Yu Mujun , Yu Haozhen , Mu Nan , Wang Yishi , Ma Heng , Yu Lu
Published: July 2022

Forkhead box (FOX) transcription factors play a crucial role in the regulation of many diseases, being an evolutionarily conserved superfamily of transcription factors. In recent years, FoxK1/2, members of its family, has been the subject of research. Even though FoxK1 and FoxK2 have some functional overlap, increasing evidence indicates that the regulatory functions of FoxK1 and FoxK2 are not the same in various physiological and disease states. It is important to understand the biological function and mechanism of FoxK1/2 for better understanding pathogenesis of diseases, predicting prognosis, and finding new therapeutic targets. There is, however, a lack of comprehensive and systematic analysis of the similarities and differences of FoxK1/2 roles in disease, prompting us to perform a literature review.
Fine Mapping and Functional Research of Key Genes for Photoperiod Sensitivity in Maize
Authors: Fei Jianbo , Jiang Qingping , Guo Mingyang , Lu Jianyu , Wang Piwu , Liu Siyan , Qu Jing , Ma Yiyong , Guan Shuyan
Published: July 2022

Maize is native to the tropics and is very sensitive to photoperiod. Planting in temperate regions with increased hours of daylight always leads to late flowering, sterility, leggy plants, and increased numbers of maize leaves. This phenomenon severely affects the utilization of tropical maize germplasm resources. The sensitivity to photoperiod is mainly reflected in differences in plant height (PH), ear height (EH), total leaf number (LN), leaf number under ear (LE), silking stage (SS), and anthesis stage (AT) in the same variety under different photoperiod conditions. These differences are more pronounced for varieties that are more sensitive to photoperiod. In the current study, a high-density genetic map was constructed from a recombinant inbred line (RIL) population containing 209 lines to map the quantitative trait loci (QTL) for photoperiod sensitivity of PH, EH, LN, LE, SS, and AT. A total of 39 QTL were identified, including three consistent major QTL. We identified candidate genes in the consensus major QTL region by combined analysis of transcriptome data, and after enrichment by GO and KEGG, we identified a total of four genes (Zm00001d006212, Zm00001d017241, Zm00001d047761, and Zm00001d047632) enriched in the plant circadian rhythm pathway (KEGG:04712). We analyzed the expression levels of these four genes, and the analysis results showed that there were significant differences in response under different photoperiod conditions for three of them (Zm00001d047761, Zm00001d006212 and Zm00001d017241). The results of functional verification showed that the expression patterns of genes rhythmically oscillated, which can affect the length of the hypocotyl and the development of the shoot apical meristem. We also found that the phenotypes of the positive plants were significantly different from the control plants when they overexpressed the objective gene or when it was knocked out, and the expression period, phase, and amplitude of the target gene also shifted. The objective gene changed its own rhythmic oscillation period, phase, and amplitude with the change in the photoperiod, thereby regulating the photoperiod sensitivity of maize. These results deepen our understanding of the genetic structure of photoperiod sensitivity and lay a foundation for further exploration of the regulatory mechanism of photoperiod sensitivity.
A Probabilistic and Syntactic Account of Variable Clitic Agreement in Spanish Double Object Constructions
Authors: Guajardo Gustavo
Published: July 2022

In Spanish clitic-doubling constructions, the clitic should agree in number with its coreferential doubled noun phrase. However, the present corpus analysis with data from 21 Spanish varieties reveals that, under certain structural configurations, number agreement is not always realized on the third-person dative clitic. In fact, the data shows that non-agreement appears to be the norm when the indirect object is a lexical noun phrase (77 vs. 23%). In this paper, I investigate two possible explanations for this phenomenon: (i) a processing accountviaan attraction effect and (ii) a syntactic account based on intervention effects. These two hypotheses make clear and testable predictions that I examine by means of conditional inference trees and Bayesian generalized mixed-effects logistic regression modeling. The results of the statistical analyses are incompatible with an intervention account because this type of phenomenon is not sensitive to semantic features of the intervening element or to the true controller of agreement. Thus, I propose that the data is best analyzed as the interplay between attraction and the morphosyntax of the unmarked. In Spanish, this results in attraction effects from the DO in the unmarked word order and inanimate IOs showing a sort of differential dative marking, where animate IOs show a preference for full agreement. The findings reported herein show evidence of a complex and highly dynamic agreement mechanism of the clitic and highlight the probabilistic nature of morphosyntactic processes.
When Parents Fail to Mind the Child: Lower Mentalizing in Parents Who Maltreat Their Children
Authors: Rosso Anna Maria
Published: July 2022

Mentalization is considered an essential ability for social cognition as well as a crucial competency in parenting to further the development of internal structures that are decisive for self organization and affect regulation in children. Yet, few empirical studies have investigated whether, and to what extent, parents who maltreat their children poorly mentalize. The aim of this research was to study the mentalization ability in a group of parents who maltreated their children and had been referred by the Courts for Child Custody and Parenting Plan Evaluation (Group 1), and in a comparison, non-clinical group of parents (Group 2). Adult Attachment Interview (AAI), rated in terms of both the Berkeley AAI System and the Reflective Functioning Scale was administered. Group 1 had severely impaired reflective functioning (RF) in 83.3% of cases, whilst impaired RF was found in only 12.5% of Group 2 parents. For the most part, parents in Group 1 showed Negative Reflective Functioning, systematically resisting taking a reflective stance, and the parents who most severely maltreated their children showed distorted and/or self-serving passages associated with a particular type of dismissing pattern of attachment (DS2) based on the derogation of attachment. The frequent occurrence of derogation in these parents likely explains how much the devaluation of relationships and attachment needs, presumably acquired during childhood with defensive purposes and in order to exclude the pain and perception of emotional weakness from awareness, hinders the capacity to care for children in the full respect of their needs.
Network Modeling of Complex Time-Dependent Changes in Patient Adherence to Adjuvant Endocrine Treatment in ER+ Breast Cancer
Authors: Shinn Eileen H. , Busch Brooke E. , Jasemi Neda , Lyman Cole A. , Toole J. Tory , Richman Spencer C. , Symmans William Fraser , Chavez-MacGregor Mariana , Peterson Susan K. , Broderick Gordon
Published: July 2022

Early patient discontinuation from adjuvant endocrine treatment (ET) is multifactorial and complex: Patients must adapt to various challenges and make the best decisions they can within changing contexts over time. Predictive models are needed that can account for the changing influence of multiple factors over time as well as decisional uncertainty due to incomplete data. AtlasTi8 analyses of longitudinal interview data from 82 estrogen receptor-positive (ER+) breast cancer patients generated a model conceptualizing patient-, patient-provider relationship, and treatment-related influences on early discontinuation. Prospective self-report data from validated psychometric measures were discretized and constrained into a decisional logic network to refine and validate the conceptual model. Minimal intervention set (MIS) optimization identified parsimonious intervention strategies that reversed discontinuation paths back to adherence. Logic network simulation produced 96 candidate decisional models which accounted for 75% of the coordinated changes in the 16 network nodes over time. Collectively the models supported 15 persistent end-states, all discontinued. The 15 end-states were characterized by median levels of general anxiety and low levels of perceived recurrence risk, quality of life (QoL) and ET side effects. MIS optimization identified 3 effective interventions: reducing general anxiety, reinforcing pill-taking routines, and increasing trust in healthcare providers. Increasing health literacy also improved adherence for patients without a college degree. Given complex regulatory networks’ intractability to end-state identification, the predictive models performed reasonably well in identifying specific discontinuation profiles and potentially effective interventions.
Development and Evaluation of Orthographic Knowledge Awareness Scale for Children Aged 6–12 Years
Authors: Xie Yachun , Xu Qu , Liu Liying , Yao Mengmeng , Liu Panting , Tong Meiling , Hong Qin , Chi Xia
Published: July 2022

Objective

This study primarily aimed to develop an orthographic knowledge awareness scale in Mandarin for children aged 6–12 years. Related factors affecting orthographic knowledge awareness in children were analyzed, and a basis for individualized intervention was provided to improve reading and writing.

Methods

A conceptual framework for orthographic knowledge awareness in children aged 6–12 years was determined through a detailed reading of the literature on Chinese character orthography, combined with qualitative interviews of the target population and consultation with experts. The orthographic knowledge awareness scale initially consisted of three versions: for grades 1–2 (210 items), grades 3–4 (207 items), and grades 5–6 (220 items), accumulating a total of 637 items. The initial scale was then used for the study involving children aged 6–12 years in Maanshan City, Jiangsu Province. Various approaches to screening items were comprehensively used to determine the formal version of the orthographic knowledge awareness scale. The official scale was ultimately used to conduct the third round of surveys among 1,354 children aged 6–12 years in ordinary primary schools located in 5 cities in Jiangsu Province, namely, Changzhou, Lianyungang, Nantong, Xuzhou, and Yangzhou. The reliability, validity, and discriminating power of the formal scale were evaluated.

Results

A total of 360 items were included in the formal version of the orthographic knowledge awareness scale. The formal scale was divided into three versions for grades 1–2, 3–4, and 5–6. Each grade version consisted of 120 items. The scale was composed of the stroke awareness test, radical awareness test, and left–right reversal test. The cumulative variance contribution rates of grades 1–2, 3–4, and 5–6 were 82.47, 61.71, and 64.19%, respectively. The Cronbach's α coefficients of the three-grade version of the scale were 0.989, 0.946, and 0.938; the split-half reliability coefficients were 0.925, 0.766, and 0.847; and the test–retest reliability coefficients were 0.847, 0.895, and 0.8928, respectively.

Conclusion

The proposed orthographic knowledge awareness scale for children aged 6–12 years exhibits good reliability and validity. The formal scale consisted of two dimensions: identification of left–right reversal at the stroke and radical levels and the left–right reversal at the whole character level. The two dimensions can more comprehensively reflect the ability of children to discriminate orthographic structures.
The Inhibitory Effect of the Deregulation Short-Sale on Private Equity Placement
Authors: Wang Panna , Su Chun , Xu Botao
Published: July 2022

In countries with a high degree of equity concentration, such as China, the second type of agency problem is serious in which major shareholders of listed companies encroach on the interests of small and medium shareholders through private placement. As a financial transaction system, the short-selling mechanism has the function of external corporate governance. Therefore, this paper examines the impact of relaxing short-selling controls on companies’ private placements. Based on the quasi-natural experiment of China’s gradual relaxation of short-selling controls since 2010, a double-difference model (DID) test is constructed to find that relaxing short-selling controls reduces companies’ private placement tendency and amount, and this effect is mainly reflected in samples with a higher degree of equity checks and balances. Further analysis found that when the size of the company’s financing constraints is different, the impact of relaxing short-selling control on the company’s private placement tendency and amount is different; when the chairman and the general manager have two positions, relaxing short-selling control reduces the company’s private placement options, but it has a negative impact on the company’s private placement. There is no difference in the impact of the company’s private placement amount. It can be excluded that the relaxation of short-selling control suppresses the company’s placement through financing constraints and corporate governance mechanisms. Compared to a good information environment, when the company’s information environment is poor, relaxing short-selling controls reduces the company’s private placement tendency and amount. Significantly, it shows that the relaxation of short-selling control policy and supervision inhibits the company’s private placement through the information environment mechanism, and promotes the sustainable development of enterprises. It not only improves the literature in the field of short-selling mechanism affecting corporate behavior, but it also enriches the research on the transfer of benefits of private placement of companies.