bluuebunny/crossref_metadata_2025 huggingface dataset:
CRIPTO Is a Marker of Chemotherapy-Induced Stem Cell Expansion in Non-Small Cell Lung Cancer
Authors: Francescangeli Federica , De Angelis Maria Laura , Rossi Rachele , Sette Giovanni , Eramo Adriana , Boe Alessandra , Guardiola Ombretta , Tang Tao , Yu Shi-Cang , Minchiotti Gabriella , Zeuner Ann
Published: June 2022

Chemotherapy is the mainstay for the treatment of non-small cell lung cancer (NSCLC). However, NSCLC cells are either intrinsically chemoresistant or rapidly develop therapy resistance. Cancer stem cells (CSCs) are widely recognized as the cell population responsible for resistance to systemic therapies, but the molecular responses of CSCs to chemotherapeutic agents are largely unknown. We identified the embryonic protein CRIPTO in stem cell-enriched spheroid cultures of adenocarcinoma (AC) and squamous cell carcinoma (SCC) derived from NSCLC surgical specimens. The CRIPTO-positive population had increased clonogenic capacity and expression of stem cell-related factors. Stemness-related properties were also obtained with forced CRIPTO expression, whereas CRIPTO downregulation resulted in cell cycle blockade and CSCs death. Cell populations positive and negative for CRIPTO expression were interconvertible, and interfering with their reciprocal equilibrium resulted in altered homeostasis of cell expansion both in spheroid cultures and in tumor xenografts. Chemotherapy treatment of NSCLC cells resulted in reduction of cell number followed by increased CRIPTO expression and selective survival of CRIPTO-positive cells. In NSCLC tumor xenografts, chemotherapeutic agents induced partial cell death and tumor stabilization followed by CRIPTO overexpression and tumor progression. Altogether, these findings indicate CRIPTO as a marker of lung CSCs possibly implicated in cancer cell plasticity and post-chemotherapy tumor progression.
IGH Translocations in Chinese Patients With Chronic Lymphocytic Leukemia: Clinicopathologic Characteristics and Genetic Profile
Authors: Li Qinlu , Xing Shugang , Zhang Heng , Mao Xiao , Xiao Min , Wang Ying
Published: June 2022

Immunoglobulin heavy chain translocations (IGH-t) have occasionally been reported in Chinese patients with chronic lymphocytic leukemia (CLL). The objective of the present study was to identify the clinicopathologic features of patients with IGH-t CLL and compare them with those of patients with non-IGH-t CLL. We performed fluorescence in situ hybridization (FISH) based on a routine CLL prognostic FISH panel using IGH, IGH-BCL2, BCL3, IGH-CMYC, and BCL6 FISH probes. Furthermore, we retrospectively evaluated the clinical features of 138 newly diagnosed CLL patients via chromosome banding analysis (CBA), FISH, and targeted next-generation sequencing. IGH-t was identified in 25 patients (18.1%). Patients with IGH-t CLL had lower flow scores than those with non-IGH-t CLL. The most frequent translocation was t(14;18) (10 patients), followed by t(14;19) (3 patients), and t(2;14)(p13;q32), t(7;14)(q21.2;q12), t(9;14)(p13;q32) (3 patients). The remaining nine patients included three with abnormal karyotypes without translocation involving 14q32, four with a normal karyotype, and two who failed CBA. The most frequently concomitant FISH-detected aberrations were 13q deletion, followed by +12 and TP53 deletion, while one case involved ATM deletion. Complex karyotypes were detected in five patients with IGH-t CLL, in whom all partner genes were non-BCL2. Available mutational information indicated that KMT2D mutation was the most frequent mutation among tested 70 patients, while TP53 mutation was the most frequent mutation in the IGH-t group. Moreover, the IGH-t group had higher FBXW7 (P=0.014) and ATM (P=0.004) mutations than the non-IGH-t group, and this difference was statistically significant. Our study demonstrates that IGH-t is not uncommon among Chinese CLL patients, and that its partner genes are multiple. The gene mutational profile of the IGH-t group was distinct from that of the non-IGH-t group, and the concomitant chromosomal abnormalities within the IGH-t CLL group differed. Thus, identification of IGH-t and its partner genes in CLL patients may help further refine risk stratification and strengthen the accurate management in CLL patients.
RETRACTED: Exosomes From Cancer-Associated Mesenchymal Stem Cells Transmit TMBIM6 to Promote the Malignant Behavior of Hepatocellular Carcinoma via Activating PI3K/AKT Pathway
Authors: Shang Chuzhi , Ke Mi , Liu Lin , Wang Cong , Liu Yufang , Zheng Xin
Published: June 2022

Objective

Cancer-associated mesenchymal stem cells (MSCs) regulate the progression of cancers through exosome-delivered components, while few studies are conducted on hepatocellular carcinoma (HCC). This study aimed to evaluate the effect of exosomes from HCC-associated MSCs (HCC-MSCs) on HCC cellular functions and the potential regulatory mechanism.

Methods

HCC cells (Huh7 and PLC) were cultured normally or co-cultured with HCC-MSCs, HCC-MSCs plus GW4869, or HCC-MSC-derived exosomes; then mRNA sequencing and RT-qPCR validation were conducted. Subsequently, candidate genes were sorted out and modified in HCC cells. Next, TMBIM6-modified HCC-MSCs were used to treat HCC cells.

Results

Both HCC-MSCs and their derived exosomes promoted proliferation, invasion, sphere formation ability but suppressed apoptosis in HCC cells (all p < 0.05); however, the effect of HCC-MSCs on these cellular functions was repressed by exosome inhibitor (GW4869). Subsequently, TMBIM6, EEF2, and PRDX1 were sorted out by mRNA sequencing and RT-qPCR validation as candidate genes implicated in the regulation of HCC cellular functions by HCC-MSC-derived exosomes. Among them, TMBIM6 had a potent effect (all p < 0.05), while EEF2 and PRDX1 had less effect on regulating HCC cell viability and invasion. Next, direct silencing TMBIM6 repressed viability, sphere formation, invasion, epithelial–mesenchymal transition (EMT), and PI3K/AKT pathway but promoted apoptosis in HCC cells; however, overexpressing TMBIM6 showed the opposite effect. Furthermore, incubating with exosomes from TMBIM6-modified HCC-MSCs presented a similar effect as direct TMBIM6 modification in HCC cells.

Conclusion

HCC-MSC-derived exosomes transmit TMBIM6 to promote malignant behavior via PI3K/AKT pathway in HCC.
The Value of Preoperative Local Symptoms in Prognosis of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: A Retrospective, Multicenter Cohort Study
Authors: Yeh Hsin-Chih , Chang Chao-Hsiang , Fang Jen-Kai , Chen I-Hsuan Alan , Lin Jen-Tai , Hong Jian-Hua , Huang Chao-Yuan , Wang Shian-Shiang , Chen Chuan-Shu , Lo Chi-Wen , Yu Chih-Chin , Tseng Jen-Shu , Lin Wun-Rong , Jou Yeong-Chin , Cheong Ian-Seng , Jiang Yuan-Hong , Tsai Chung-You , Hsueh Thomas Y. , Chen Yung-Tai , Huang Hsu-Che , Tsai Yao-Chou , Lin Wei-Yu , Wu Chia-Chang , Lin Po-Hung , Lin Te-Wei , Wu Wen-Jeng
Published: June 2022

Purpose

We aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC).

Methods

This retrospective study consisted of 2,662 UTUC patients treated at 15 institutions in Taiwan from 1988 to 2019. Clinicopathological data were retrospectively collected for analysis by the Taiwan UTUC Collaboration Group. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS). The prognostic value of preoperative local symptoms in OS, CSS, DFS, and BRFS was investigated using Cox proportional hazards models.

Results

The median follow-up was 36.6 months. Among 2,662 patients, 2,130 (80.0%) presented with hematuria and 398 (15.0%) had symptomatic hydronephrosis at diagnosis. Hematuria was associated with less symptomatic hydronephrosis (p <0.001), more dialysis status (p = 0.027), renal pelvic tumors (p <0.001), and early pathological tumor stage (p = 0.001). Symptomatic hydronephrosis was associated with female patients (p <0.001), less dialysis status (p = 0.001), less bladder cancer history (p <0.001), ureteral tumors (p <0.001), open surgery (p = 0.006), advanced pathological tumor stage (p <0.001), and postoperative chemotherapy (p = 0.029). Kaplan-Meier analysis showed that patients with hematuria or without symptomatic hydronephrosis had significantly higher rates of OS, CSS, and DFS (all p <0.001). Multivariate analysis confirmed that presence of hematuria was independently associated with better OS (HR 0.789, 95% CI 0.661–0.942) and CSS (HR 0.772, 95% CI 0.607–0.980), while symptomatic hydronephrosis was a significant prognostic factor for poorer OS (HR 1.387, 95% CI 1.142–1.683), CSS (HR 1.587, 95% CI 1.229–2.050), and DFS (HR 1.378, 95% CI 1.122–1.693).

Conclusions

Preoperative local symptoms were significantly associated with oncological outcomes, whereas symptomatic hydronephrosis and hematuria had opposite prognostic effects. Preoperative symptoms may provide additional information on risk stratification and perioperative treatment selection for patients with UTUC.
High DNMT1 Expression in Stromal Fibroblasts Promotes Angiogenesis and Unfavorable Outcome in Locally Advanced Breast Cancer Patients
Authors: Al-Kharashi Layla A. , Tulbah Asma , Arafah Maria , Eldali Abdelmonneim M. , Al-Tweigeri Taher , Aboussekhra Abdelilah
Published: June 2022

Background

Active breast cancer-associated fibroblasts (CAFs) play a leading role in breast carcinogenesis through promoting angiogenesis and resistance to therapy. Consequently, these active stromal cells have significant influence on patient outcome. Therefore, we explored here the role of the DNA methyltransferase 1 (DNMT1) protein in CAF-dependent promotion of angiogenesis as well as the prognostic power of DNMT1 level in both cancer cells and their adjacent CAFs in locally advanced breast cancer patients.

Methods

We applied immunohistochemistry to evaluate the level of DNMT1 in breast cancer tissues and their adjacent normal counterparts. Quantitative RT-PCR and immunoblotting were performed to investigate the role of DNMT1 in regulating the expression of pro-angiogenic genes in active CAFs and also their response to the DNMT1 inhibitors decitabine (DAC) as well as eugenol.

Results

We have shown that DNMT1 controls the pro-angiogenic potential of CAFs both in vitro and in vivo through positive regulation of the expression/secretion of 2 important pro-angiogenic factors VEGF-A and IL-8 as well as their upstream effectors mTOR and HIF-1α. To confirm this, we have shown that these DNMT1-related pro-angiogenic effects were suppressed by 2 DNMT1 inhibitors decitabine and eugenol. Interestingly, in a cohort of 100 tumors from locally advanced breast cancer patients (LABC), we have shown that high expression of DNMT1 in tumor cells and their adjacent stromal fibroblasts is correlated with poor survival of these patients.

Conclusion

DNMT1 upregulation in breast stromal fibroblasts promotes angiogenesis via IL-8/VEGF-A upregulation, and correlates well with poor survival of LABC patients.
Association of Tumor Size With Myometrial Invasion, Lymphovascular Space Invasion, Lymph Node Metastasis, and Recurrence in Endometrial Cancer: A Meta-Analysis of 40 Studies With 53,276 Patients
Authors: Jin Xiaoying , Shen Chunjuan , Yang Xiaodi , Yu Yayuan , Wang Jianzhang , Che Xuan
Published: June 2022

Background

Myometrial invasion (MI), lymphovascular space invasion (LVSI), and lymph node metastasis (LNM) have been found to have independent prognostic factors in endometrial cancer. Tumor size has practical advantages in endometrial cancer. The cutoff values for tumor size conformed with current literature. More and more studies inferred that tumor size >20 mm showed a strong correlation. However, the relationship between tumor size >20 mm and MI, LVSI, LNM, recurrence, and overall survival (OS) remains controversial, and no meta-analysis has been conducted. Therefore, a systematic review and meta-analysis should be performed to discuss this issue later on.

Methods

Relevant articles were collected from PubMed, EMBASE, and Cochrane Library databases from January 1990 to June 2021. The predictive value of tumor size >20 mm in endometrial cancer was studied, and data were pooled for meta-analysis using Review Manager 5.1. Additionally, the odds ratio (OR) was analyzed, and cumulative analyses of hazard ratio (HR) and their corresponding 95% CI were conducted.

Results

A total of 40 articles with 53,276 endometrial cancer patients were included in the meta-analysis. It contained 7 articles for MI, 6 for LVSI, 21 for LNM, 7 for recurrence, and 3 for OS. Primary tumor size >20 mm was significantly associated with depth of MI (OR = 5.59, 95% CI [5.02, 6.23], p < 0.001), positive LVSI (OR = 3.35, 95% CI [2.34, 4.78], p < 0.001), positive LNM (OR = 4.11, 95% CI [3.63, 4.66], p < 0.001), and recurrence (OR = 3.52, 95% CI [2.39, 5.19], p < 0.001). Tumor size >20 mm was also related to OS via meta-synthesis of HR in univariate survival (HR 2.13, 95% CI [1.28, 3.53], p = 0.003). There was no significant publication bias in this study by funnel plot analysis.

Conclusion

Primary tumor size >20 mm was an independent predictive factor for the depth of MI, positive LVSI, positive LNM, recurrence, and poor OS. Therefore, it is more important to take into account the value of tumor size in the clinicopathological staging of endometrial carcinoma. Tumor size >20 mm should be integrated into the intraoperative algorithm for performing a full surgical staging. Well-designed and multicenter studies, with a larger sample size, are still required to verify the findings.
Underexpression of LINC00173 in TCF3/PBX1-Positive Cases Is Associated With Poor Prognosis in Children With B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: May-Hau Didier Ismael , Bárcenas-López Diego Alberto , Núñez-Enríquez Juan Carlos , Bekker-Méndez Vilma Carolina , Beltrán-Anaya Fredy Omar , Jiménez-Hernández Elva , Ortíz-Maganda Mónica Patricia , Guerra-Castillo Francisco Xavier , Medina-Sanson Aurora , Flores-Lujano Janet , Martín-Trejo Jorge Alfonso , Peñaloza-González José Gabriel , Velázquez-Aviña Martha Margarita , Torres-Nava José Refugio , Hernández-Echáurregui Gabriela Alicia , Espinosa-Elizondo Rosa Martha , Gutiérrez-Rivera María de Lourdes , Sanchez-Hernandez Rodrigo , Pérez-Saldívar María Luisa , Flores-Villegas Luz Victoria , Merino-Pasaye Laura Elizabeth , Duarte-Rodríguez David Aldebarán , Mata-Rocha Minerva , Sepúlveda-Robles Omar Alejandro , Rosas-Vargas Haydeé , Hidalgo-Miranda Alfredo , Mejía-Aranguré Juan Manuel , Jiménez-Morales Silvia
Published: June 2022

Background

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent pediatric cancer worldwide. Despite improvements in treatment regimens, approximately 20% of the cases cannot be cured, highlighting the necessity for identifying new biomarkers to improve the current clinical and molecular risk stratification schemes. We aimed to investigate whether LINC00173 is a biomarker in ALL and to explore its expression level in other human cancer types.

Methods

A nested case–control study including Mexican children with BCP-ALL was conducted. LINC00173 expression was evaluated by qRT-PCR using hydrolysis probes. To validate our findings, RNA-seq expression data from BCP-ALL and normal tissues were retrieved from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) repositories, respectively. LINC00173 expression was also evaluated in solid tumors by downloading available data from The Cancer Genome Atlas (TCGA).

Results

A lower expression of LINC00173 in BCP-ALL cases compared to normal subjects was observed (p < 0.05). ALL patients who carry the TCF3/PBX1 fusion gene displayed lower expression of LINC00173 in contrast to other BCP-ALL molecular subtypes (p < 0.04). LINC00173 underexpression was associated with a high risk to relapse (HR = 1.946, 95% CI = 1.213–3.120) and die (HR = 2.073, 95% CI = 1.211–3.547). Patients with TCF3/PBX1 and underexpression of LINC00173 had the worst prognosis (DFS: HR = 12.24, 95% CI = 5.04–29.71; OS: HR = 11.19, 95% CI = 26–32). TCGA data analysis revealed that underexpression of LINC00173 is also associated with poor clinical outcomes in six new reported tumor types.

Conclusion

Our findings suggest that LINC00173 is a biomarker of poor prognosis in BCP-ALL and other types of cancer. We observed an association between the expression of LINC00173 and TCF3/PBX1 and the risk to relapse and die in BCP-ALL, which is worse in TCF3/PBX1-positive cases displaying underexpression of LINC00173. Experimental studies are needed to provide insight into the LINC00173 and TCF3/PBX relationship.
In Bilinguals' Hands: Identification of Bilingual, Preverbal Infants at Risk for Language Delay
Authors: Lüke Carina , Ritterfeld Ute , Liszkowski Ulf
Published: June 2022

Studies with monolingual infants show that the gestural behavior of 1–2-year-olds is a strong predictor for later language competencies and, more specifically, that the absence of index-finger pointing at 12 months seems to be a valid indicator for risk of language delay (LD). In this study a lack of index-finger pointing at 12 months was utilized as diagnostic criterion to identity infants with a high risk for LD at 24 months in a sample of 42 infants growing up bilingually. Results confirm earlier findings from monolinguals showing that 12-month-olds who point with the extended index finger have an advanced language status at 24 months and are less likely language delayed than infants who only point with the whole hand and do not produce index-finger points at 12 months.
The Correlation Between ABPM Parameters and Left Ventricular Hypertrophy in Pediatric Essential Hypertension
Authors: Wu Haojie , Shi Lin , Lin Yao , Zheng Tong
Published: June 2022

Objective

To explore the association of dipping pattern and blood pressure load with left ventricular hypertrophy (LVH) in pediatric essential hypertension.

Materials and Methods

Through an echocardiography monitor and an ambulatory blood pressure monitor of 425 children and adolescents diagnosed with essential hypertension with no treatment received, we identified 140 cases of LVH. Grouping patients according to LVH (LVH, N = 140; n-LVH, N = 285), we further evaluated their ambulatory blood pressure monitoring (ABPM) parameters by comparing dipping patterns between groups. A multivariable logistic regression analysis was used to determine the effect of blood pressure load on LVH.

Results

No significant difference was found in systolic or diastolic blood pressure dipping patterns between groups (P = 0.161, P = 0.139). However, compared to the n-LVH group, the LVH group presented significant elevated nighttime systolic blood pressure (SBP) (P < 0.05), while nighttime DBP remained stable (P = 0.391), resulting in higher daytime and nighttime SBP loads, higher nighttime DBP load, and higher 24-h SBP load (P < 0.05). Notably, our multivariable logistic regression has shown that this trend of 24-h SBP load acts independently as a critical risk factor for LVH.

Conclusion

Collectively, we observed a correlation between BP load and LVH in pediatric hypertension. Our data demonstrated that SBP load has a more significant weight in LVH progression, and 24-h SBP load, in particular, acts as a critical early prognostic parameter for LVH in pediatric hypertension.
Integrated Chemical Interpretation and Network Pharmacology Analysis to Reveal the Anti-Liver Fibrosis Effect of Penthorum chinense
Authors: Du Zenan , Huang Doudou , Shi Pengjie , Dong Zhiying , Wang Xiujuan , Li Mengshuang , Chen Wansheng , Zhang Feng , Sun Lianna
Published: June 2022

Liver fibrosis is a disease with complex pathological mechanisms. Penthorum chinense Pursh (P. chinense) is a traditional Chinese medicine (TCM) for liver injury treatment. However, the pharmacological mechanisms of P. chinense on liver fibrosis have not been investigated and clarified clearly. This study was designed to investigate the chemicals in P. chinense and explore its effect on liver fibrosis. First, we developed a highly efficient method, called DDA-assisted DIA, which can both broaden mass spectrometry (MS) coverage and MS2 quality. In DDA-assisted DIA, data-dependent acquisition (DDA) and data-independent acquisition (DIA) were merged to construct a molecular network, in which 1,094 mass features were retained in Penthorum chinense Pursh (P. chinense). Out of these, 169 compounds were identified based on both MS1 and MS2 analysis. After that, based on a network pharmacology study, 94 bioactive compounds and 440 targets of P. chinense associated with liver fibrosis were obtained, forming a tight compound–target network. Meanwhile, the network pharmacology experimental results showed that multiple pathways interacted with the HIF-1 pathway, which was first identified involved in P. chinense. It could be observed that some proteins, such as TNF-α, Timp1, and HO-1, were involved in the HIF-1 pathway. Furthermore, the pharmacological effects of P. chinense on these proteins were verified by CCl4-induced rat liver fibrosis, and P. chinense was found to improve liver functions through regulating TNF-α, Timp1, and HO-1 expressions. In summary, DDA-assisted DIA could provide more detailed compound information, which will help us to annotate the ingredients of TCM, and combination with computerized network pharmacology provided a theoretical basis for revealing the mechanism of P. chinense.
Advances in Fingerprint Analysis for Standardization and Quality Control of Herbal Medicines
Authors: Noviana Eka , Indrayanto Gunawan , Rohman Abdul
Published: June 2022

Herbal drugs or herbal medicines (HMs) have a long-standing history as natural remedies for preventing and curing diseases. HMs have garnered greater interest during the past decades due to their broad, synergistic actions on the physiological systems and relatively lower incidence of adverse events, compared to synthetic drugs. However, assuring reproducible quality, efficacy, and safety from herbal drugs remains a challenging task. HMs typically consist of many constituents whose presence and quantity may vary among different sources of materials. Fingerprint analysis has emerged as a very useful technique to assess the quality of herbal drug materials and formulations for establishing standardized herbal products. Rather than using a single or two marker(s), fingerprinting techniques take great consideration of the complexity of herbal drugs by evaluating the whole chemical profile and extracting a common pattern to be set as a criterion for assessing the individual material or formulation. In this review, we described and assessed various fingerprinting techniques reported to date, which are applicable to the standardization and quality control of HMs. We also evaluated the application of multivariate data analysis or chemometrics in assisting the analysis of the complex datasets from the determination of HMs. To ensure that these methods yield reliable results, we reviewed the validation status of the methods and provided perspectives on those. Finally, we concluded by highlighting major accomplishments and presenting a gap analysis between the existing techniques and what is needed to continue moving forward.
Targeting Thyroid Hormone/Thyroid Hormone Receptor Axis: An Attractive Therapy Strategy in Liver Diseases
Authors: Tang Qianyu , Zeng Min , Chen Linxi , Fu Nian
Published: June 2022

Thyroid hormone/thyroid hormone receptor (TH/TR) axis is characterized by TH with the assistance of plasma membrane transporters to combine with TR and mediate biological activities. Growing evidence suggests that TH/TR participates in plenty of hepatic metabolism. Thus, this review focuses on the role of the TH/TR axis in the liver diseases. To be specific, the TH/TR axis may improve metabolic-associated fatty liver disease, hepatitis, liver fibrosis, and liver injury while exacerbating the progression of acute liver failure and alcoholic liver disease. Also, the TH/TR axis has paradoxical roles in hepatocellular carcinoma. The TH/TR axis may be a prospecting target to cure hepatic diseases.
Liposomes are Poorly Absorbed via Lung Lymph After Inhaled Administration in Sheep
Authors: Ibrahim Jibriil P , Haque Shadabul , Bischof Robert J , Whittaker Andrew K , Whittaker Michael R , Kaminskas Lisa M
Published: June 2022

Enhancing the delivery of therapeutic agents to the lung lymph, including drugs, transfection agents, vaccine antigens and vectors, has the potential to significantly improve the treatment and prevention of a range of lung-related illnesses. One way in which lymphatic delivery can be optimized is via the use of nanomaterial-based carriers, such as liposomes. After inhaled delivery however, there is conflicting information in the literature regarding whether nanomaterials can sufficiently access the lung lymphatics to have a therapeutic benefit, in large part due to a lack of reliable quantitative pharmacokinetic data. The aim of this work was to quantitatively evaluate the pulmonary lymphatic pharmacokinetics of a model nanomaterial-based drug delivery system (HSPC liposomes) in caudal mediastinal lymph duct cannulated sheep after nebulized administration to the lungs. Liposomes were labelled with 3H-phosphatidylcholine to facilitate evaluation of pharmacokinetics and biodistribution in biological samples. While nanomaterials administered to the lungs may access the lymphatics via direct absorption from the airways or after initial uptake by alveolar macrophages, only 0.3 and 0.001% of the 3H-lipid dose was recovered in lung lymph fluid and lymph cell pellets (containing immune cells) respectively over 5 days. This suggests limited lymphatic access of liposomes, despite apparent pulmonary bioavailability of the 3H-lipid being approximately 17%, likely a result of absorption of liberated 3H-lipid after breakdown of the liposome in the presence of lung surfactant. Similarly, biodistribution of 3H in the mediastinal lymph node was insignificant after 5 days. These data suggest that liposomes, that are normally absorbed via the lymphatics after interstitial administration, do not access the lung lymphatics after inhaled administration. Alternate approaches to maximize the lung lymphatic delivery of drugs and other therapeutics need to be identified.
Ethnomedicinal, Phytochemical and Pharmacological Investigations of Tetradenia riparia (Hochst.) Codd (Lamiaceae)
Authors: Panda Sujogya Kumar , Gazim Zilda Cristiani , Swain Shasank S. , Bento Marisa Cassia Vieira de Araujo , Sena Jéssica da Silva , Mukazayire Marie Jeanne , Van Puyvelde Luc , Luyten Walter
Published: June 2022

Tetradenia ripariaHochsteter codd. (Lamiaceae) in its native African continent, is considered one of the most popular aromatic medicinal plants. In folk medicine it may be used as an infusion to treat respiratory problems, cough, headache, stomach pain, diarrhea, fever, malaria, and dengue; and in the form of compresses it is applied for the relief of headaches and toothaches. The speciesT. ripariahas been researched for decades to isolate and identify chemical constituents present in extracts or essential oil obtained from the leaves, floral buds, or stems of this plant. The present study reviews the scientific literature on ethnomedicinal, phytochemical, and pharmacological aspects ofT. riparia. We discuss issues related to the botanical and geographical description of the species, ethnobotanical uses, phytochemical studies on its essential oil and extracts, and biological activities ofT. riparia.Several compounds have already been isolated from leaves, such as ibozol, 7α-hydroxyroileanone, 1′,2′-dideacetylboronolide, 8(14),15-sandaracopimaradiene-7α,18-diol; 5,6-dihydro-α-pyrone and α-pyrone. Terpenes predominated in the essential oil, comprising monoterpenes, sesquiterpenes, diterpenes, hydrocarbons, and oxygenates. Most phytocompounds were isolated from the leaves and flower buds, namely fenchone, 14-hydroxy-9-epi (E)-caryophyllene, 9β, 13β-epoxy-7-abietene, and 6,7-dehydroroileanone. These compounds provide the species a high pharmacological potential, with antimicrobial, antioxidant, antitumor, analgesic, anti-leishmania, anti-tuberculosis, and anti-parasitic activities. Therefore, this species is a promising herbal medicine.
The Application of UHPLC-HRMS for Quality Control of Traditional Chinese Medicine
Authors: Ma Jieyao , Li Kailin , Shi Silin , Li Jian , Tang Sunv , Liu LiangHong
Published: June 2022

UHPLC-HRMS (ultra-high-performance liquid chromatography-high resolution mass spectrometry) is a new technique that unifies the application of UHPLC with HRMS. Because of the high sensitivity and good separation ability of UHPLC and the sensitivity of HRMS, this technique has been widely used for structure identification, quantitative determination, fingerprint analysis, and elucidation of the mechanisms of action of traditional Chinese medicines (TCMs) in recent years. This review mainly outlines the advantages of using UHPLC-HRMS and provides a survey of the research advances on UHPLC-HRMS for the quality control of TCMs.
The Time-Course Changes in Knee Flexion Range of Motion, Muscle Strength, and Rate of Force Development After Static Stretching
Authors: Nakamura Masatoshi , Suzuki Yusuke , Yoshida Riku , Kasahara Kazuki , Murakami Yuta , Hirono Tetsuya , Nishishita Satoru , Takeuchi Kosuke , Konrad Andreas
Published: June 2022

Previous studies have shown that longer-duration static stretching (SS) interventions can cause a decrease in muscle strength, especially explosive muscle strength. Furthermore, force steadiness is an important aspect of muscle force control, which should also be considered. However, the time course of the changes in these variables after an SS intervention remains unclear. Nevertheless, this information is essential for athletes and coaches to establish optimal warm-up routines. The aim of this study was to investigate the time course of changes in knee flexion range of motion (ROM), maximal voluntary isometric contraction (MVIC), rate of force development (RFD), and force steadiness (at 5 and 20% of MVIC) after three 60-s SS interventions. Study participants were sedentary healthy adult volunteers (n = 20) who performed three 60-s SS interventions of the knee extensors, where these variables were measured before and after SS intervention at three different periods, i.e., immediately after, 10 min, and 20 min the SS intervention (crossover design). The results showed an increase in ROM at all time points (d = 0.86–1.01). MVIC was decreased immediately after the SS intervention (d = −0.30), but MVIC showed a recovery trend for both 10 min (d = −0.17) and 20 min (d = −0.20) after the SS intervention. However, there were significant impairments in RFD at 100 m (p = 0.014, F = 6.37, ηp2 = 0.101) and 200 m (p < 0.01, F = 28.0, ηp2 = 0.33) up to 20 min after the SS intervention. Similarly, there were significant impairments in force steadiness of 5% (p < 0.01, F = 16.2, ηp2 = 0.221) and 20% MVIC (p < 0.01, F = 16.0, ηp2 = 0.219) at 20 min after the SS intervention. Therefore, it is concluded that three 60-s SS interventions could increase knee flexion ROM but impair explosive muscle strength and muscle control function until 20 min after the SS intervention.
Ancient Tethyan Vicariance and Long-Distance Dispersal Drive Global Diversification and Cryptic Speciation in the Red Seaweed Pterocladiella
Authors: Boo Ga Hun , Leliaert Frederik , Le Gall Line , Coppejans Eric , De Clerck Olivier , Van Nguyen Tu , Payri Claude E. , Miller Kathy Ann , Yoon Hwan Su
Published: June 2022

We investigated the globally distributed red algal genus Pterocladiella, comprising 24 described species, many of which are economically important sources of agar and agarose. We used DNA-based species delimitation approaches, phylogenetic, and historical biogeographical analyses to uncover cryptic diversity and infer the drivers of biogeographic patterns. We delimited 43 species in Pterocladiella, of which 19 are undescribed. Our multigene time-calibrated phylogeny and ancestral area reconstruction indicated that Pterocladiella most likely originated during the Early Cretaceous in the Tethys Sea. Ancient Tethyan vicariance and long-distance dispersal have shaped current distribution patterns. The ancestor of Eastern Pacific species likely arose before the formation of the formidable Eastern Pacific Barrier—a first confirmation using molecular data in red algae. Divergences of Northeast and Southeast Pacific species have been driven by the Central American Seaway barrier, which, paradoxically, served as a dispersal pathway for Atlantic species. Both long- and short-distance dispersal scenarios are supported by genetic relationships within cosmopolitan species based on haplotype analysis. Asymmetrical distributions and the predominance of peripatry and sympatry between sister species suggest the importance of budding speciation in Pterocladiella. Our study highlights the underestimation of global diversity in these crucial components of coastal ecosystems and provides evidence for the complex evolution of current species distributions.
Differential Growth Responses of Alternanthera philoxeroides as Affected by Submergence Depths
Authors: Jing Shufang , Zhang Xiaoping , Niu Hangang , Lin Feng , Ayi Qiaoli , Wan Binna , Ren Xinyi , Su Xiaolei , Shi Shaohua , Liu Songping , Zeng Bo
Published: June 2022

Global climate change has resulted in an increase in intensity and frequency of flooding, plants living in lowlands, and shore areas have to confront submergence caused by flooding, submergence-tolerant plants usually respond by adopting either escape or quiescence strategies. While certain plants exhibit a changeover from escape strategy upon partial submergence to quiescence strategy under complete shallow submergence, it remains unknown whether plants completely submerged at different water depths would adjust their strategies to cope with the change in submergence depth. Alternanthera philoxeroides is an ideal species to explore this adjustment as it is widely distributed in flood-disturbed habitats and exhibits an escape strategy when completely submerged in shallow waters. We investigated the responses of A. philoxeroides in terms of morphology, anatomy, and non-structural carbohydrate metabolism by conducting experiments using a series of submergence depths (0, 2, 5, and 9 m). During the submergence treatment, environmental factors such as light, dissolved oxygen, and temperature for submerged plants were kept constant. The results showed that A. philoxeroides plants submerged at depth of 2 m presented an escape strategy via fast stem elongation, extensive pith cavity development, and small biomass loss. However, the retarded stem elongation, reduced pith cavity transverse area, and increased biomass loss along the water depth gradient indicated that A. philoxeroides altered its growth response as water depth increased from 2 to 9 m. It is found that the changeover of response strategies occurred at higher submergence depths (5–9 m). Based on the results of our experiments, we demonstrated that water depth played an important role in driving the change in strategy. The water-depth-dependent growth performance of A. philoxeroides would benefit the species in habit exploration and exploitation. Further studies should focus on the performances of plants when submerged at varied water depths with different light climates and dissolved oxygen content, and how water depths drive the response behaviors of the submerged plants.
Nested miRNA Secondary Structure Is a Unique Determinant of miR159 Efficacy in Arabidopsis
Authors: Imran Muhammad , Liu Tengfei , Wang Zheng , Wang Min , Liu Shulin , Gao Xinyan , Wang Anning , Liu Songfeng , Tian Zhixi , Zhang Min
Published: June 2022

MicroRNAs (miRNAs) are 20- to 24-nucleotide small RNAs, and whenever a pri-miRNA precursor includes another miRNA precursor, and both of these precursors may generate independent non overlapping mature miRNAs, we called them nested miRNAs. However, the functional and regulatory roles of nested miRNA structures in plants are still unknown. In this study, the Arabidopsis nested miR159a structure, which consists of two nested miRNAs, miR159a.1, and miR159a.2, was used as a model to determine miRNA-mediated gene silencing in plants. Complementation analysis of nested miR159a structures revealed that the miR159a structure can differentially complement the mir159ab phenotype, and a duplex nested structure in the tail end region of the pre-miR159a fold back may have a possible dominant function, indicating the importance of the flanking sequence of the stem in the cleavage of the mature miRNA. Furthermore, continuously higher expression of the miR159a.2 duplex in the severe leaf curl phenotype indicates that miR159a.2 is functional in Arabidopsis and suggests that in plants, a miRNA precursor may encode multiple regulatory small RNAs. Taken together, our study demonstrates that the nested miR159a structure regulated by duplex mutations of miR159a has a unique pattern and provides novel insight into silencing efficacy of Arabidopsis miR159a.
Xyloglucan Biosynthesis: From Genes to Proteins and Their Functions
Authors: Julian Jordan D. , Zabotina Olga A.
Published: June 2022

The plant’s recalcitrant cell wall is composed of numerous polysaccharides, including cellulose, hemicellulose, and pectin. The most abundant hemicellulose in dicot cell walls is xyloglucan, which consists of a β-(1- > 4) glucan backbone with α-(1- > 6) xylosylation producing an XXGG or XXXG pattern. Xylose residues of xyloglucan are branched further with different patterns of arabinose, fucose, galactose, and acetylation that varies between species. Although xyloglucan research in other species lag behind Arabidopsis thaliana, significant advances have been made into the agriculturally relevant species Oryza sativa and Solanum lycopersicum, which can be considered model organisms for XXGG type xyloglucan. In this review, we will present what is currently known about xyloglucan biosynthesis in A. thaliana, O. sativa, and S. lycopersicum and discuss the recent advances in the characterization of the glycosyltransferases involved in this complex process and their organization in the Golgi.
The Maternal Donor of Chrysanthemum Cultivars Revealed by Comparative Analysis of the Chloroplast Genome
Authors: Xu Yufen , Liao Borong , Ostevik Kate L. , Zhou Hougao , Wang Fenglan , Wang Baosheng , Xia Hanhan
Published: June 2022

Chrysanthemum (Chrysanthemum morifolium Ramat) is an important floricultural crop and medicinal herb. Modern chrysanthemum cultivars have complex genetic backgrounds because of multiple cycles of hybridization, polyploidization, and prolonged cultivation. Understanding the genetic background and hybrid origin of modern chrysanthemum cultivars can provide pivotal information for chrysanthemum genetic improvement and breeding. By now, the origin of cultivated chrysanthemums remains unclear. In this study, 36 common chrysanthemum cultivars from across the world and multiple wild relatives were studied to identify the maternal donor of modern chrysanthemum. Chloroplast (cp) genomes of chrysanthemum cultivars were assembled and compared with those of the wild relatives. The structure of cp genomes was highly conserved among cultivars and wild relatives. Phylogenetic analyses based on the assembled cp genomes showed that all chrysanthemum cultivars grouped together and shared 64 substitutions that were distinct from those of their wild relatives. These results indicated that a diverged lineage of the genus Chrysanthemum, which was most likely an extinct or un-sampled species/population, provided a maternal source for modern cultivars. These findings provide important insights into the origin of chrysanthemum cultivars, and a source of valuable genetic markers for chrysanthemum breeding programs.
The Predictive Effects of Family and Individual Wellbeing on University Students' Online Learning During the COVID-19 Pandemic
Authors: Zhu Xiaoqin , Chu Carman K. M. , Lam Yee Ching
Published: June 2022

The COVID-19 pandemic has significantly changed university students' life routines, such as prolonged stay at home and learning online without prior preparation. Identifying factors influencing student online learning has become a great concern of educators and researchers. The present study aimed to investigate whether family wellbeing (i.e., family support and conflict) would significantly predict university students' online learning effectiveness indicated by engagement and gains. The mediational role of individual wellbeing such as life satisfaction and sleep difficulties was also tested. This study collected data from 511 undergraduate students (Mean age = 20.04 ± 1.79 years, 64.8% female students) via an online survey. Structural equation modeling analysis revealed positive effects of family support on students' learning engagement and gains through the mediational effects of life satisfaction and sleep difficulties. In contrast to our expectation, family conflict during the pandemic also positively predicted students' learning gains, which, however, was not mediated by individual wellbeing. The findings add value to the existing literature by delineating the inter-relationships between family wellbeing, individual wellbeing, and online learning effectiveness. The study also sheds light on the unique meaning of family conflict, which needs further clarification in future studies.
Modeling Chinese Teachers’ Efficacies for the Teaching of Integrated STEM With Interdisciplinary Communication and Epistemic Fluency
Authors: Lin Pei-Yi , Chai Ching Sing , Di Weifeng , Wang Xingwei
Published: June 2022

Engineering design is a core activity in integrated science, technology, engineering, and mathematics (STEM) education. During the design process, teachers should possess interdisciplinary communication capacities to collaborate with their peers who are teaching different subjects and have epistemic fluency to comprehend multiple ways of subject matter knowing for the collective design of high-quality integrated STEM (iSTEM) lessons. This is especially so for the online mode of instruction during and after the pandemic. Teachers’ efficacies for interdisciplinary communication and epistemic fluency have rarely been explored. In this study, we aimed to examine primary school, junior high school, and high school STEM teachers’ (N = 483) efficacies for daily instruction, student engagement, interdisciplinary communication, epistemic fluency, and technological pedagogical engineering knowledge (TPEK) and designing integrated STEM instruction. An exploratory factor analysis (EFA) (n = 155) and a subsequent confirmatory factor analysis (CFA) (n = 328) were used to validate the measurement and structural model. Next, a structural equation model (SEM) was employed to examine whether these variables were reliable predictors of teachers’ integrated STEM instruction. The survey was validated with good reliabilities and the structural equation modeling supported most of the hypotheses. Statistically, the results also showed that teachers’ general efficacies for daily teaching and students’ engagement predicted their interdisciplinary communication, epistemic fluency, and TPEK. Teachers’ interdisciplinary communication predicted their epistemic fluency, TPEK, and iSTEM. Teachers’ epistemic fluency also predicted their TPEK and iSTEM. In addition, multi-group analyses were used to test the measurement invariance of the scale and to compare the latent means between the genders and subject matters. The results of the various analyses confirmed that the measurement model appeared to be equivalent across the genders and subject matters examined. Genders and subject matters did not significantly differ in any of the measured variables. The results from this study indicate that teachers’ epistemic fluency and interdisciplinary communication play essential roles in advancing their TPEK and iSTEM. Hence, this study suggests that teacher professional development should focus on enhancing teacher epistemic fluency through interdisciplinary collaboration to support the development of TPEK and iSTEM instruction.
Deep Learning in Neuroimaging: Overcoming Challenges With Emerging Approaches
Authors: Smucny Jason , Shi Ge , Davidson Ian
Published: June 2022

Deep learning (DL) is of great interest in psychiatry due its potential yet largely untapped ability to utilize multidimensional datasets (such as fMRI data) to predict clinical outcomes. Typical DL methods, however, have strong assumptions, such as large datasets and underlying model opaqueness, that are suitable for natural image prediction problems but not medical imaging. Here we describe three relatively novel DL approaches that may help accelerate its incorporation into mainstream psychiatry research and ultimately bring it into the clinic as a prognostic tool. We first introduce two methods that can reduce the amount of training data required to develop accurate models. These may prove invaluable for fMRI-based DL given the time and monetary expense required to acquire neuroimaging data. These methods are (1)transfer learning− the ability of deep learners to incorporate knowledge learned from one data source (e.g., fMRI data from one site) and apply it toward learning from a second data source (e.g., data from another site), and (2)data augmentation (via Mixup)− a self-supervised learning technique in which “virtual” instances are created. We then discussexplainable artificial intelligence(XAI), i.e., tools that reveal what features (and in what combinations) deep learners use to make decisions. XAI can be used to solve the “black box” criticism common in DL and reveal mechanisms that ultimately produce clinical outcomes. We expect these techniques to greatly enhance the applicability of DL in psychiatric research and help reveal novel mechanisms and potential pathways for therapeutic intervention in mental illness.
Inflammatory Cytokines Changed in Patients With Depression Before and After Repetitive Transcranial Magnetic Stimulation Treatment
Authors: Wang Qiang , Zeng Lingyun , Hong Wenjuan , Luo Mingying , Zhao Nan , Hu Xiaofen , Shi Meili , Qiu Jing , Shen Yanmin , Teng Xiuju , Min Haiying , Liu Weiqing
Published: June 2022

Studies have found that repetitive transcranial magnetic stimulation rTMS can produce antidepressant effects by affecting inflammatory cytokines in patients with depression, which plays a key role in the therapeutic mechanism of antidepressants. This study aimed to explore the changes in inflammatory cytokine levels in patients with depression after 4 weeks of rTMS treatment to determine the possible antidepressant mechanism of rTMS. This prospective, double-blind, pseudo-stimulus-controlled study was conducted, and a total of 57 patients with depression and 30 healthy controls were recruited. Patients were randomly divided into the active rTMS (n = 29) and sham rTMS groups (n = 28). The Hamilton Depression Scale was used to evaluate depressive symptoms and their severity. The serum levels of seven inflammatory cytokines were measured using enzyme-linked immunosorbent assay. Inflammatory cytokines include high-sensitivity C-reactive protein (CRP-hc); tumor necrosis factor (TNF-α); interferon (IFN-γ); interleukin-2 (IL-2); interleukin-4 (IL-4); interleukin-6 (IL-6); and interleukin-8 (IL-8). At baseline, TNF-α (F = 36.699, p < 0.001), IFN-γ (F = 8.907, p < 0.001), IL-4 (F = 66.256, p < 0.001), and IL-2 (F = 9.162, p < 0.001) levels in the depression group were significantly different from those of healthy controls. In the self-control analysis of the active rTMS group, the levels of IL-2 and CRP-hc increased significantly after 2 and 12 weeks of treatment. In the sham-rTMS group, IFN-γ increased after 2 and 12 weeks of treatment. Our results revealed that the changes in inflammatory cytokines after rTMS treatment showed different patterns compared to the sham group, suggesting that the antidepressant effect of rTMS may be related to changes in inflammatory cytokines.