bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and Functioning of China’s Dryland Ecosystems in a Changing Environment
Authors: Li Changjia , Fu Bojie , Wang Shuai , Stringer Lindsay C. , Zhou Wenxin , Lu Tong , Wu Xutong , Hu Rina , Ren Zhuobing 
Published: February 2024

AbstractChina has one of the largest dryland areas worldwide, covering 6.6 million km2 and supporting approximately 580 million people. Conflicting findings showing a drier China’s drylands with increasing aridity and observed greenness indicate the complexity of environmental processes, highlighting a pressing research need to improve understanding of how active dryland processes, ecosystem structure and functioning will alter. This chapter synthesizes the changes, impacts, and their drivers in China’s dryland ecosystems. Results from analyses covering the period 2000–2015 showed that 58.69% of the vegetated area exhibited an increase in vegetation greenness, cover, and productivity, while 4.29% of those showed a decrease in all three aspects. However, 37.02% of the vegetated area showed inconsistent trends in vegetation greenness, cover, and productivity, suggesting high uncertainty in estimations of vegetation dynamics in drylands. China’s drylands are nevertheless at risk of expansion and could pass an irreversible tipping point with increasing aridity, particularly in the country’s semi-arid regions. Nitrogen enrichment and overgrazing generally reduce plant species diversity. Wind erosion, water erosion, salinization, and freeze–thaw erosion are typical processes of desertification in China’s drylands. Large-scale ecological restoration projects enhance greening and ecosystem services of China’s drylands, but also impose substantial pressure on these water-limited environments. Future research is needed to examine interactions among different drivers of environmental change (e.g., the relationships between CO2 fertilization and increased aridity). Such research could usefully include complex systems approaches to link patterns and processes across spatial and time scales, and long-term experiments on physical‐chemical‐biological process interactions.
Dryland Dynamics in the Mediterranean Region
Authors: Zeng Hongwei , Wu Bingfang , Elnashar Abdelrazek , Fu Zhijun 
Published: February 2024

AbstractMediterranean drylands are rich in biodiversity and play an important role in global ecosystem sustainable management. This study summarizes the characteristics, dynamic change, and change drivers of Mediterranean drylands. The drylands showed strong spatial heterogeneity, hyperarid and arid regions were dominant in North Africa and West Asia, and semiarid and dry subhumid regions were widely distributed in European countries. Mediterranean dryland is experiencing a warming trend that would become stronger under representative concentration pathways (RCP) 4.5 and 8.5, which would increase the risk of land degradation and desertification. Arid North Africa and West Asia faced rapid population growth that put considerable pressure on food supply and water consumption. The conflicts among land, water, food, and the ecosystem intensified under the warming trend. The significant expansion of cropland and urbanization was widely observed in arid areas, such as Egypt, while the rotation of land reclamation, degradation, abandonment, and reclamation was observed in arid areas and caused large-scale cross-border migration. The Mediterranean region had low food self-sufficiency due to a booming population, and the crop structure of cash crops was dominant. The expansion of cropland also significantly increased the water consumption in the arid area of the Mediterranean region, and water consumption increased by 684.54 × 106 m3 from 2000 to 2020 in Egypt. More robust models and fine spatial resolution data should be developed for the sustainable development of Mediterranean drylands.
Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling
Authors: Wei Zhi-Xing , Cai Xing-Xing , Fei Yu-Dong , Wang Qian , Hu Xiao-Liang , Li Cheng , Hou Jian-Wen , Yang Yu-Li , Chen Tai-Zhong , Xu Xiao-Lei , Wang Yue-Peng , Li Yi-Gang 
Published: February 2024

AbstractAtrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.
Graphical Abstract
FBP1 inhibits NSCLC stemness by promoting ubiquitination of Notch1 intracellular domain and accelerating degradation
Authors: He Tianyu , Wang Yanye , Lv Wang , Wang Yiqing , Li Xinye , Zhang Qingyi , Shen Han-Ming , Hu Jian 
Published: February 2024

AbstractThe existence of cancer stem cells is widely acknowledged as the underlying cause for the challenging curability and high relapse rates observed in various tumor types, including non-small cell lung cancer (NSCLC). Despite extensive research on numerous therapeutic targets for NSCLC treatment, the strategies to effectively combat NSCLC stemness and achieve a definitive cure are still not well defined. The primary objective of this study was to examine the underlying mechanism through which Fructose-1,6-bisphosphatase 1 (FBP1), a gluconeogenic enzyme, functions as a tumor suppressor to regulate the stemness of NSCLC. Herein, we showed that overexpression of FBP1 led to a decrease in the proportion of CD133-positive cells, weakened tumorigenicity, and decreased expression of stemness factors. FBP1 inhibited the activation of Notch signaling, while it had no impact on the transcription level of Notch 1 intracellular domain (NICD1). Instead, FBP1 interacted with NICD1 and the E3 ubiquitin ligase FBXW7 to facilitate the degradation of NICD1 through the ubiquitin–proteasome pathway, which is independent of the metabolic enzymatic activity of FBP1. The aforementioned studies suggest that targeting the FBP1-FBXW7-NICD1 axis holds promise as a therapeutic approach for addressing the challenges of NSCLC recurrence and drug resistance.
FDA-approved disulfiram as a novel treatment for aggressive leukemia
Authors: Karsa Mawar , Xiao Lin , Ronca Emma , Bongers Angelika , Spurling Dayna , Karsa Ayu , Cantilena Sandra , Mariana Anna , Failes Tim W. , Arndt Greg M. , Cheung Laurence C. , Kotecha Rishi S. , Sutton Rosemary , Lock Richard B. , Williams Owen , de Boer Jasper , Haber Michelle , Norris Murray D. , Henderson Michelle J. , Somers Klaartje 
Published: February 2024

Abstract
Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better and safer treatments for acute leukemia are urgently needed, standard drug development pipelines are lengthy and drug repurposing therefore provides a promising approach. Our previous evaluation of FDA-approved drugs for their antileukemic activity identified disulfiram, used for the treatment of alcoholism, as a candidate hit compound. This study assessed the biological effects of disulfiram on leukemia cells and evaluated its potential as a treatment strategy. We found that disulfiram inhibits the viability of a diverse panel of acute lymphoblastic and myeloid leukemia cell lines (n = 16) and patient-derived xenograft cells from patients with poor outcome and treatment-resistant disease (n = 15). The drug induced oxidative stress and apoptosis in leukemia cells within hours of treatment and was able to potentiate the effects of daunorubicin, etoposide, topotecan, cytarabine, and mitoxantrone chemotherapy. Upon combining disulfiram with auranofin, a drug approved for the treatment of rheumatoid arthritis that was previously shown to exert antileukemic effects, strong and consistent synergy was observed across a diverse panel of acute leukemia cell lines, the mechanism of which was based on enhanced ROS induction. Acute leukemia cells were more sensitive to the cytotoxic activity of disulfiram than solid cancer cell lines and non-malignant cells. While disulfiram is currently under investigation in clinical trials for solid cancers, this study provides evidence for the potential of disulfiram for acute leukemia treatment.

Key messages

Disulfiram induces rapid apoptosis in leukemia cells by boosting oxidative stress.

Disulfiram inhibits leukemia cell growth more potently than solid cancer cell growth.

Disulfiram can enhance the antileukemic efficacy of chemotherapies.

Disulfiram strongly synergises with auranofin in killing acute leukemia cells by ROS induction.

We propose testing of disulfiram in clinical trial for patients with acute leukemia.
Funktionelle Ergebnisse und Wiederaufnahme von Sport, Arbeit und Alltagsaktivitäten nach Revision eines Monoschlittens im Vergleich zur Primärimplantation eines Mono- und Doppelschlittens
Authors: Scheele Christian B. , Pietschmann Matthias F. , Wagner Thomas C. , Müller Peter E. 
Published: February 2024

Zusammenfassung
Hintergrund
Neben dem etablierten Doppelschlitten (bikondylärer Kniegelenksersatz [TKA]) hat sich, bei geeigneter Patientenselektion, der Monoschlitten (unikondylärer Kniegelenksersatz [UKA]) in der operativen Therapie der Gonarthrose bewährt. In klinischen Studien zeigt er überlegene funktionelle Ergebnisse bei geringeren Komplikationsraten. Im klinischen Alltag sind diese Vorteile, insbesondere bei jüngeren, sportlich und beruflich aktiven Patienten gegen den Nachteil einer erhöhten Revisionsrate abzuwiegen. Das Ergebnis einer ggf. früheren Revision erscheint hier relevant.

Fragestellung
Ziel dieser Studie war es, sowohl funktionelles Ergebnis als auch den Zeitraum bis zur Wiederaufnahme von Alltags-, beruflichen und sportlichen Aktivitäten nach Revision eines Mono- auf einen Doppelschlitten denen von primären Mono- und Doppelschlitten anhand einer Matched-Pair-Vergleichsanalyse gegenüberzustellen.

Methodik
Die Studie basierte auf einer Matched-Pair-Vergleichsanalyse zu zwei definierten Zeitpunkten und verglich stets 28 Patienten, die entweder die Revision eines Mono- auf einen Doppelschlitten, eine primäre Implantation eines Monoschlittens oder die eines Doppelschlittens erhielten. Die Patienten beantworteten im Rahmen eines standardisierten Follow-ups den Oxford Knee Score, den UCLA-Score, den Knee Society Score sowie den WOMAC-Score. Darüber hinaus wurden die postoperative Patientenzufriedenheit sowie die Wiederaufnahme von Alltags-, beruflichen und sportlichen Aktivitäten standardisiert erfasst und eine klinische Untersuchung durchgeführt.

Ergebnisse
Die vier untersuchten Funktions-Scores zeigten einen gemeinsamen Trend zugunsten der Monoschlitten, gefolgt von den primären Doppelschlitten und Revisionsdoppelschlitten. Die Unterschiede der Revisionsdoppelschlitten und der primären Doppelschlitten waren hierbei nicht signifikant. Allerdings lagen die Ergebnisse der konvertierten Monoschlitten 3,2 Jahre nach der letzten Operation signifikant unter denen der primären Monoschlitten. Die Rückkehr zur beruflichen und sportlichen Aktivität gelang nach Monoschlitten tendenziell am frühesten, gefolgt von Doppelschlitten und Revisionsgruppe. In allen Gruppen zeigte sich ein Trend zur Durchführung sog. Low-Impact-Sportarten.

Diskussion
Die funktionellen Ergebnisse eines konvertierten Monoschlittens zeigen sich denen der Primärimplantation auf Basis des 3‑Jahres-Follow-ups signifikant unterlegen. Die Rückkehr in Beruf, Sport und Alltag dauerte nach Revision tendenziell länger als nach Primärimplantation eines Mono- oder Doppelschlittens.
Family-oriented versus career seekers: mixture regression separation
Authors: Delsalle Lara , Birulin Oleksii 
Published: February 2024

AbstractUsing a finite mixture regression approach, we identify two groups of individuals, family- and career-oriented. Depending on whether the employment status is treated as a binomial or trinomial (with part-time work) variable, 55–70% of women and 4–10% of men belong to the family-oriented group. Children variables are the main source of differences between the two identified groups and between the family-oriented group and the average woman. Treating all women as one group leads to averaged-out estimates of children effects and underestimates the importance of part-time work for family-oriented women. Our results are important for studying women’s labour supply and for designing policies aimed at encouraging women’s labour market involvement.
A green-footprint approach for parallel multiclass analysis of contaminants in roasted coffee via LC-HRMS
Authors: España Amórtegui Julio César , Ekroth Susanne , Pekar Heidi , Guerrero Dallos Jairo Arturo 
Published: February 2024

AbstractThe development and validation of a simple, comprehensive, and environment-friendly procedure to determine pesticide residues, naturally occurring and processing contaminants in roasted coffee is presented. A solid-liquid extraction of pesticides and mycotoxins with ethyl acetate and the concurrent partition of acrylamide to an aqueous phase follows a parallel analytical strategy that requires a single analytical portion to determine contaminants that are typically analyzed by dedicated single residue methods. The partition rules the lipids out of the aqueous extract before an “in-tube” dispersive solid phase microextraction (dSPME) for acrylamide retention. This is followed by the elution with buffer prior to injection. This extract is independently introduced into the system front end followed by the injection of the compounds from the organic phase, yet all spotted in the same run. A novel liquid chromatography high-resolution mass spectrometry (LC-HRMS) method setup enables the quantification of 186 compounds at 10 µg/kg, 226 at 5 µg/kg, and the acrylamide at 200 µg/kg for a total of 414 molecules, with acceptable recoveries (70–120%) and precision (RSD < 20%) making this strategy significantly faster and cost-effective than the dedicated single residue methods. Even though the presence of chlorpyrifos, acrylamide, and ochratoxin A was confirmed on samples of different origins, the findings were below the limit of quantification. During the storage of raw coffee, no proof of masking of OTA was found; however, condensation with glucose was evidenced during thermal processing experiments with sucrose by using stable isotope labeling (SIL). No detected conjugates were found in roasted nor in commercial sugar-added torrefacto samples, an industrial processing usually carried out above the decomposition temperature of the disaccharide.
Graphical abstract
Targeting monoamine oxidase A: a strategy for inhibiting tumor growth with both immune checkpoint inhibitors and immune modulators
Authors: Ma Yifan , Chen Hanmu , Li Hui , Zhao Zhite , An Qingling , Shi Changhong 
Published: February 2024

AbstractMonoamine oxidase A (MAOA) is a membrane-bound mitochondrial enzyme present in almost all vertebrate tissues that catalyzes the degradation of biogenic and dietary-derived monoamines. MAOA is known for regulating neurotransmitter metabolism and has been implicated in antitumor immune responses. In this review, we retrospect that MAOA inhibits the activities of various types of tumor-associated immune cells (such as CD8+ T cells and tumor-associated macrophages) by regulating their intracellular monoamines and metabolites. Developing novel MAOA inhibitor drugs and exploring multidrug combination strategies may enhance the efficacy of immune governance. Thus, MAOA may act as a novel immune checkpoint or immunomodulator by influencing the efficacy and effectiveness of immunotherapy. In conclusion, MAOA is a promising immune target that merits further in-depth exploration in preclinical and clinical settings.
Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma
Authors: Chen Anan , Yu Zhiwu , Ma Na , Lu Xinyu , Zhang Yajing , Xu Weikang , Wang Yiyue , Xie Jiayi , Qin Yuqi , Mo Guoheng , Wu Sha , Hou Jinlin , Zhu Wei 
Published: February 2024

AbstractT-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for tumor treatment, yet hindered by tumor immune evasion resulting in poor therapeutic efficacy. The introduction of ferroptosis-targeted inducers offers a potential solution, as they empower T cells to induce ferroptosis and exert influence over the tumor microenvironment. Atovaquone (ATO) stands as a prospective pharmaceutical candidate with the potential to target ferroptosis, effectively provoking an excessive generation and accumulation of reactive oxygen species (ROS). In this study, we evaluated the effectiveness of a combination therapy comprising ATO and TCR-T cells against hepatocellular carcinoma (HCC), both in vitro and in vivo. The results of lactate dehydrogenase and cytokine assays demonstrated that ATO enhanced cytotoxicity mediated by AFP-specific TCR-T cells and promoted the release of IFN-γ in vitro. Additionally, in an established HCC xenograft mouse model, the combined therapy with low-dose ATO and TCR-T cells exhibited heightened efficacy in suppressing tumor growth, with no apparent adverse effects, comparable to the results achieved through monotherapy. The RNA-seq data unveiled a significant activation of the ferroptosis-related pathway in the combination therapy group in comparison to the TCR-T cells group. Mechanistically, the synergy between ATO and TCR-T cells augmented the release of IFN-γ by TCR-T cells, while concurrently elevating the intracellular and mitochondrial levels of ROS, expanding the labile iron pool, and impairing the integrity of the mitochondrial membrane in HepG2 cells. This multifaceted interaction culminated in the potentiation of ferroptosis within the tumor, primarily induced by an excess of ROS. In summary, the co-administration of ATO and TCR-T cells in HCC exhibited heightened vulnerability to ferroptosis. This heightened susceptibility led to the inhibition of tumor growth and the stimulation of an anti-tumor immune response. These findings suggest that repurposing atovaquone for adoptive cell therapy combination therapy holds the potential to enhance treatment outcomes in HCC.
Investigating the immunological function of alpha-2-glycoprotein 1, zinc-binding in regulating tumor response in the breast cancer microenvironment
Authors: Hanamura Toru , Yokoyama Kozue , Kitano Shigehisa , Kagamu Hiroshi , Yamashita Makiko , Terao Mayako , Okamura Takuho , Kumaki Nobue , Hozumi Katsuto , Iwamoto Takayuki , Honda Chikako , Kurozumi Sasagu , Richer Jennifer K. , Niikura Naoki 
Published: February 2024

Abstract
Background
Alpha-2-glycoprotein 1, zinc-binding (ZAG), a secreted protein encoded by the AZGP1 gene, is structurally similar to HLA class I. Despite its presumed immunological function, little is known about its role in tumor immunity. In this study, we thus aimed to determine the relationship between the expression of AZGP1/ZAG and the immunological profiles of breast cancer tissues at both the gene and protein level.

Methods
Using a publicly available gene expression dataset from a large-scale breast cancer cohort, we conducted gene set enrichment analysis (GSEA) to screen the biological processes associated with AZGP1. We analyzed the correlation between AZGP1 expression and immune cell composition in breast cancer tissues, estimated using CIBERSORTx. Previously, we evaluated the infiltration of 11 types of immune cells for 45 breast cancer tissues using flow cytometry (FCM). ZAG expression was evaluated by immunohistochemistry on these specimens and analyzed for its relationship with immune cell infiltration. The action of ZAG in M1/M2 polarization models using primary cultures of human peripheral blood mononuclear cells (PBMC)-derived macrophage (Mφ) was analyzed based on the expression of M1/M2 markers (CD86, CD80/CD163, MRC1) and HLA class I/II by FCM.

Results
AZGP1 expression was negatively correlated with multiple immunological processes and specific immune cell infiltration including Mφ M1 using GSEA and CIBERSORTx. ZAG expression was associated with decreased infiltration of monocytes/macrophages, non-classical monocytes, and myeloid-derived suppressor cells in tumor tissues assessed using FCM. In in vitro analyses, ZAG decreased the expression of CD80, CD163, MRC1, and HLA classes I/II in the M1 polarization model and the expression of CD163 and MRC1 in the M2 polarization model.

Conclusion
ZAG is suggested to be a novel immunoregulatory factor affecting the Mφ phenotype in breast cancer tissues.
Longitudinal plasma proteomic analysis identifies biomarkers and combinational targets for anti-PD1-resistant cancer patients
Authors: Tan Qiaoyun , Gao Ruyun , Zhang Xiaomei , Yang Jianliang , Xing Puyuan , Yang Sheng , Wang Dan , Wang Guibing , Wang Shasha , Yao Jiarui , Zhang Zhishang , Tang Le , Yu Xiaobo , Han Xiaohong , Shi Yuankai 
Published: February 2024

AbstractThe response rate of anti-PD1 therapy is limited, and the influence of anti-PD1 therapy on cancer patients is unclear. To address these challenges, we conducted a longitudinal analysis of plasma proteomic changes with anti-PD1 therapy in non-small cell lung cancer (NSCLC), alveolar soft part sarcoma (ASPS), and lymphoma patients. We included 339 plasma samples before and after anti-PD1 therapy from 193 patients with NSCLC, ASPS, or lymphoma. The plasma proteins were detected using data-independent acquisition-mass spectrometry and customable antibody microarrays. Differential proteomic characteristics in responders (R) and non-responders (NR) before and after anti-PD1 therapy were elucidated. A total of 1019 proteins were detected using our in-depth proteomics platform and distributed across 10–12 orders of abundance. By comparing the differential plasma proteome expression between R and NR groups, 50, 206, and 268 proteins were identified in NSCLC, ASPS, and lymphoma patients, respectively. Th17, IL-17, and JAK-STAT signal pathways were identified upregulated in NR group, while cellular senescence and transcriptional misregulation pathways were activated in R group. Longitudinal proteomics analysis revealed the IL-17 signaling pathway was downregulated after treatment. Consistently, many proteins were identified as potential combinatorial therapeutic targets (e.g., IL-17A and CD22). Five noninvasive biomarkers (FLT4, SFTPB, GNPTG, F5, and IL-17A) were further validated in an independent lymphoma cohort (n = 39), and another three noninvasive biomarkers (KIT, CCL3, and TNFSF1) were validated in NSCLC cohort (n = 76). Our results provide molecular insights into the anti-PD1 therapy in cancer patients and identify new therapeutic strategies for anti-PD1-resistant patients.