bluuebunny/crossref_metadata_2025 huggingface dataset:
Indigenous eco-archaeology: past, present, and future of environmental stewardship in central coastal California
Authors: Apodaca Alec , Sanchez Gabriel M. , Sigona Alexii , Grone Michael , Lopez Valentin , Lightfoot Kent G.
Published: September 2024

The Amah Mutsun Tribal Band (AMTB) has stewarded terrestrial and aquatic resources in central California since time immemorial. Successive waves of European and Euro-American colonization have sought to suppress and erode AMTB's relationship with land, stewardship, and natural resources. The Tribe has mobilized anthropological and historical ecological data that demonstrate the effect of long-term Indigenous stewardship through cultural burning and other resource stewardship strategies. These Indigenous landscape legacies have influenced ecosystem structure and the sustainability of culturally important species. This paper focuses on the process of bridging archaeological research with contemporary stewardship efforts related to protecting, preserving, and caring for Tribal cultural heritage that exists from a landscape perspective. The collaborative research has helped clarify the record of Tribal relationships with the environment and how those relationships have changed due to colonial land use regimes. In doing so, we highlight how an archaeological research program can be a building point of access to ancestral places, which is a critical step in Tribal-led initiatives of restoring traditional resource management and ecological resilience of plant and animal life on public lands. In addition, we discuss the benefits and limitations of applying eco-archaeological research toward Tribal environmental stewardship.
Association of dietary habits with general and abdominal obesity in Korean children and adolescents: cluster analysis of nationwide population survey data
Authors: Yun Ye-Jin , Kwon Yu-Jin , Lee Yaeji , Heo Seok-Jae , Lee Ji-Won
Published: September 2024

Introduction

Childhood obesity is a growing global health concern, but few studies have investigated dietary factors specifically related to obesity and abdominal obesity in children and adolescents. Herein, we aimed to identify the dietary factors affecting childhood obesity in Korean children and adolescents.

Methods

Data from the Korea National Health and Nutrition Survey (KNHANES) VIII were analyzed using K-means clustering analysis to identify distinct clusters based on nine variables related to dietary habit, nutritional status, and nutritional education. Multiple logistic regression analysis was used to examine the association between incident obesity risk and the different clusters. We enrolled 2,290 participants aged 6-18 years, and separated them into two distinct clusters; Healthy and Unhealthy Dietary Habit Groups, clusters 1 and 2, respectively.

Results

Cluster 1 was characterized by a lower obesity prevalence, healthier dietary habits (regular breakfast consumption; fruit and vegetable, reduced total energy, and lower protein and fat intakes), and greater nutritional education than Cluster 2. After adjusting for confounders, compared with Cluster 1, Cluster 2 demonstrated a significantly higher prevalence (OR [95% CI]) of both general and abdominal obesity (1.49 [1.05–2.13], p=0.027 and 1.43 [1.09–1.88], p=0.009).

Discussion

Maintaining optimal dietary quality and patterns are crucial to prevent childhood obesity. Further research is warranted to explore specific dietary interventions tailored to different clusters to effectively address childhood obesity.
Lsm14b controls zebrafish oocyte growth by regulating polyadenylation of the mRNA poly(A) tail
Authors: Wu Xingxing , Peng Xixia , Deng Tingting , Peng Wanjun , Hu Bing , Nie Guohui
Published: September 2024

Lsm14b (LSM family member 14b) is a messenger ribonucleoprotein (mRNP) and a widely present component in eukaryotes. Lsm14b participates in oocyte development by regulating mRNA translation, however, the specific translational regulatory mechanisms remain unclear. Here, we explore the function of Lsm14b during early oocyte development and identify specific translational regulatory mechanisms. We established female-infertile lsm14b mutant zebrafish using CRISPR/Cas9. Histological examination showed that the oocyte development in the mutant zebrafish was arrested at the primary growth (PG) stage. The gene set enrichment analysis (GSEA) analysis of the transcriptome revealed that signaling pathways associated with mRNA translation suppression and mRNA poly(A) tail shortening were significantly downregulation in the mutant. The poly(A) tail length (PAT) assay confirmed the lengthen of mRNA poly(A) tail of the oocyte development-related genes zar1 and figla in the mutant. Further studies have suggested that the loss of Lsm14b triggers the unfolded protein response (UPR), which is related to abnormal translation inhibition. Our results demonstrate that Lsm14b assists in maintaining the translation-inhibited state of mRNA by regulating the length of the mRNA poly(A) tail in zebrafish early oocytes, which ensures that the mRNA synthesized and stored during the growth stage of oocytes, is necessary for the normal growth and development of oocytes.
Dispersed limitation and homogeneous selection drive the eukaryotic microbial community assembly and network stability in the coastal China sea
Authors: Chen Zhuo , Gu Ting , Sun Jun
Published: September 2024

Eukaryotic microorganisms were the key components of marine microecosystems and were involved in biogeochemical cycling processes. Although oceanographers have emphasized their importance in open oceans, the current understanding was not comprehensive enough about the assembly processes and co-occurrence network of different fraction eukaryotic microbial communities in the coastal China sea. We used co–occurrence networks and ecological process model to investigate possible ecological interactions in two fractions (small fraction 0.22–3 μm; large fraction 3–200 μm) of eukaryotes throughout different depths and geographical regions of coastal China sea. We found that environmental distance shapes the diversity of the two fractions eukaryotic microorganisms. Dispersal limitation and homogeneous selection processes were the key drivers of eukaryotic microbial community assembly. Co-occurrence network analysis showed that the networks of the 0.2–3 μm eukaryotes more nodes and edges, with more complex interactions between microorganisms, and higher network stability than that of 3–200 μm eukaryotic microorganisms. Temperature, oxygen, salinity, and nutrients play the crucial role in the abundance of two fractions eukaryotic microorganisms. These results crystallize the knowledge of eukaryotic microbes in the coastal China sea, which was essential for addressing the challenges posed by global change.
A nomogram to predict 28-day mortality in patients with sepsis combined coronary artery disease: retrospective study based on the MIMIC-III database
Authors: Gu Quankuan , Huang Ping , Yang Qiuyue , Meng Xianglin , Zhao Mingyan
Published: September 2024

Object

Establish a clinical prognosis model of coronary heart disease (CHD) to predict 28-day mortality in patients with sepsis.

Method

The data were collected retrospectively from septic patients with a previous history of coronary heart disease (CHD) from the Medical Information Mart for Intensive Care (MIMIC)-III database. The included patients were randomly divided into the training cohorts and validation cohorts. The variables were selected using the backward stepwise selection method of Cox regression, and a nomogram was subsequently constructed. The nomogram was compared to the Sequential Organ Failure Assessment (SOFA) model using the C-index, area under the receiver operating characteristic curve (AUC) over time, Net reclassification index (NRI), Integrated discrimination improvement index (IDI), calibration map, and decision curve analysis (DCA).

Result

A total of 800 patients were included in the study. We developed a nomogram based on age, diastolic blood pressure (DBP), pH, lactate, red blood cell distribution width (RDW), anion gap, valvular heart disease, peripheral vascular disease, and acute kidney injury (AKI) stage. The nomogram was evaluated using C-index, AUC, NRI, IDI, calibration plot, and DCA. Our findings revealed that this nomogram outperformed the SOFA score in predicting 28-day mortality in sepsis patients.
Deciphering the differences of bacterial communities between high- and low-productive wheat fields using high-throughput sequencing
Authors: Niu Hongjin , Yuan Min , Chen Xiaobo , Zhao Jingwei , Cui Yushuang , Song Yao , Zhou Sihao , Song Alin , Huang Yali
Published: September 2024

Microbial communities have been demonstrated to be essential for healthy and productive soil ecosystems. However, an understanding of the relationship between soil microbial community and soil productivity levels is remarkably limited. In this study, bulk soil (BS), rhizosphere soil (RS), and root (R) samples from the historical high-productive (H) and low-productive (L) soil types of wheat in Hebei province of China were collected and analyzed by high-throughput sequencing. The study highlighted the richness, diversity, and structure of bacterial communities, along with the correlation networks among different bacterial genera. Significant differences in the bacterial community structure between samples of different soil types were observed. Compared with the low-productive soil type, the bacterial communities of samples from the high-productive soil type possessed high species richness, low species diversity, complex and stable networks, and a higher relative abundance of beneficial microbes, such as Pseudoxanthomonas, unclassified Vicinamibacteraceae, Lysobacter, Massilia, Pseudomonas, and Bacillus. Further analysis indicated that the differences were mainly driven by soil organic matter (SOM), available nitrogen (AN), and electrical conductivity (EC). Overall, the soil bacterial community is an important factor affecting soil health and crop production, which provides a theoretical basis for the targeted regulation of microbes in low-productivity soil types.
Transcriptome profiling of macrophages persistently infected with human respiratory syncytial virus and effect of recombinant Taenia solium calreticulin on immune-related genes
Authors: Rivera-Toledo Evelyn , Fernández-Rojas Miguel A. , Santiago-Olivares Carlos , Cruz-Rivera Mayra , Hernández-Bautista Vania , Ávila-Horta Fernanda , Flisser Ana , Mendlovic Fela
Published: September 2024

Introduction

Human respiratory syncytial virus (hRSV) is a main cause of bronchiolitis in infants and its persistence has been described in immunocompromised subjects. However, limited evidence has been reported on the gene expression triggered by the hRSV and the effect of recombinant Taenia solium-derived calreticulin (rTsCRT).

Methods

Using a comprehensive microarray approach, we analyzed the transcriptome profile of a macrophage cell line that has supported hRSV persistence for over 150 passages. We compared the gene expression of persistently infected and non-infected macrophages. We also evaluated the effect of rTsCRT on hRSV-infected macrophage gene transcription, as well as on cytokine production and number of copies of the persistent hRSV genome.

Results

Our analysis showed that hRSV long-term virus infection significantly alters mRNA expression of antiviral, inflammatory, as well as arginine and lipid metabolism-associated genes, revealing a transcriptional signature that suggests a mixed M1/M2 phenotype. The resulting host-virus equilibrium allows for the regulation of viral replication, while evading the antiviral and proinflammatory responses. Interestingly, rTsCRT stimulus upregulated Tnfα, Il6 and Nos2 mRNA. We found increased levels of both proinflammatory cytokines and nitrite levels in the conditioned media of persistent macrophages treated with rTsCRT. This increase was associated with a significant reduction in viral genome copies.

Discussion

hRSV persistently infected macrophages retain responsiveness to external stimuli and demonstrate that the profound changes induced by viral persistence are potentially reversible. Our observations contribute to the understanding of the mechanisms related to hRSV persistence in macrophages and have implications for the development of targeted therapies to eliminate persistent infections or reduce the negative effects related with chronic inflammatory diseases associated with hRSV infection.
Antifungal metabolites of biocontrol stain LB-1 and their inhibition mechanism against Botrytis cinerea
Authors: Zhang Huan , Ji Hongliang , Liu Caiyun
Published: September 2024

Introduction

Chaetomium subaffine LB-1 is a novel biocontrol strain that produces non-volatile metabolites that inhibit the growth of Botrytis cinerea. However, the specific metabolites and antimicrobial mechanism of the strain LB-1 remains unclear.

Methods

In this study, the antifungal substances produced by strain LB-1, as well as the underlying mechanism of its inhibitory effect against B. cinerea, were explored using metabolomic and transcriptomic analysis.

Results

The results found that 45 metabolites might be the key antifungal substances, such as ouabain, ferulic acid, chlorogenic acid, spermidine, stachydrine, and stearic acid. The transcriptomic analysis indicated that the inhibition effect of LB-1 on B. cinerea resulted in the upregulation of genes related to adenosine triphosphate (ATP)-binding cassette (ABC) transporters, peroxisome, ER stress, and multiple metabolic pathways, and in downregulation of many genes associated with the synthesis of cell walls/membranes, carbohydrate metabolism, cell cycle, meiosis, and DNA replication.

Discussion

These results suggested that the inhibitory effect of strain LB-1 against B. cinerea might be due to the destroyed cell wall and membrane integrity exerted by antimicrobial substances, which affect cell metabolism and inhibit cell proliferation.
Antagonism of rhizosphere Trichoderma brevicompactum DTN19 against the pathogenic fungi causing corm rot in saffron (Crocus sativus L.) in vitro
Authors: Tian Li , Zhu Xinyu , Guo Yingqiu , Zhou Qianjun , Wang Lili , Li Wankui
Published: September 2024

Introduction

Corm rot in saffron (Crocus sativus L.) significantly impacts yield and quality. Non-toxic fungi, particularly Trichoderma species, are valuable for biological control due to their production of diverse and biologically active secondary metabolites.

Methods

This study aimed to isolate an effective antagonistic fungus against the pathogenic fungi causing corm rot in saffron. Four pathogenic fungi (Fusarium oxysporum, Fusarium solani, Penicillium citreosulfuratum, and Penicillium citrinum) were isolated from diseased saffron bulbs in Chongming. Initial screening through dual culture with these pathogens re-screening from rhizosphere soil samples of C. sativus based on its inhibitory effects through volatile, nonvolatile, and fermentation broth metabolites. The inhibitory effect of biocontrol fungi on pathogenic fungi in vitro was evaluated by morphological observation and molecular biology methods.

Results

Antagonistic fungi were identified as Trichoderma brevicompactum DTN19. F. oxysporum was identified as the most severe pathogen. SEM (scanning electron microscope) and TEM (transmission electron microscope) observations revealed that T. brevicompactum DTN19 significantly inhibited the growth and development of F. oxysporum mycelium, disrupting its physiological structure and spore formation. Additionally, T. brevicompactum DTN19 demonstrated nitrogen fixation and production of cellulase, IAA (Indole acetic acid), and siderophores. Whole-genome sequencing of strain DTN19 revealed genes encoding protease, cellulase, chitinase, β-glucosidase, siderophore, nitrogen cycle, and sulfate transporter-related proteins

Discussion

T. brevicompactum DTN19 may inhibit the propagation of pathogenic fungi by destroying their cell walls or producing antibiotics. It can also produce IAA and iron carriers, which have the potential to promote plant growth. Overall, T. brevicompactum DTN19 showed the development prospect of biological agents.
In 2024, the amyloid-cascade-hypothesis still remains a working hypothesis, no less but certainly no more
Authors: Behl Christian
Published: September 2024

The amyloid-cascade-hypothesis of the pathogenesis of Alzheimer’s disease (AD) was introduced 32 years ago, in 1992. From early on, this clear and straight forward hypothesis received a lot of attention, but also a lot of substantial criticism. Foremost, there have always been massive doubts that a complex age-associated disorder of the most intricate organ of the human body, the brain, can be explained by a linear, one-dimensional cause-and-effect model. The amyloid-cascade defines the generation, aggregation, and deposition of the amyloid beta peptide as the central pathogenic mechanism in AD, as the ultimate trigger of the disease, and, consequently, as the key pharmacological target. Certainly, the original 1992 version of this hypothesis has been refined by various means, and the ‘formulating fathers’ followed up with a few reappraisals and partly very open reflections in 2002, 2006, 2009, and 2016. However, up until today, for the supporters of this hypothesis, the central and initial steps of the cascade are believed to be driven by amyloid beta—even if now displayed somewhat more elaborate. In light of the recently published clinical results achieved with anti-amyloid antibodies, the controversy in the field about (1) the clinical meaningfulness of this approach, (2) the significance of clearance of the amyloid beta peptide, and last but not least (3) the relevance of the amyloid-cascade-hypothesis is gaining momentum. This review addresses the interesting manifestation of the amyloid-cascade-hypothesis as well as its ups and downs over the decades.
Causal effects of obstructive sleep apnea on chronic kidney disease and renal function: a bidirectional Mendelian randomization study
Authors: Hou Yawei , Li Yameng , Xiao Zhenwei , Wang Zhenguo
Published: September 2024

Background

Observational studies have suggested an association between obstructive sleep apnea (OSA), chronic kidney disease (CKD), and renal function, and vice versa. However, the results from these studies are inconsistent. It remains unclear whether there are causal relationships and in which direction they might exist.

Methods

We used a two-sample Mendelian randomization (MR) method to investigate the bidirectional causal relation between OSA and 7 renal function phenotypes [creatinine-based estimated glomerular filtration rate (eGFRcrea), cystatin C-based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), rapid progress to CKD, rapid decline of eGFR, urinary albumin to creatinine ratio (UACR) and CKD]. The genome-wide association study (GWAS) summary statistics of OSA were retrieved from FinnGen Consortium. The CKDGen consortium and UK Biobank provided GWAS summary data for renal function phenotypes. Participants in the GWAS were predominantly of European ancestry. Five MR methods, including inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were used to investigate the causal relationship. The IVW result was considered the primary outcome. Then, Cochran’s Q test and MR-Egger were used to detect heterogeneity and pleiotropy. The leave-one-out analysis was used for testing the stability of MR results. RadialMR was used to identify outliers. Bonferroni correction was applied to test the strength of the causal relationships (p < 3.571 × 10−3).

Results

We failed to find any significant causal effect of OSA on renal function phenotypes. Conversely, when we examined the effects of renal function phenotypes on OSA, after removing outliers, we found a significant association between BUN and OSA using IVW method (OR: 2.079, 95% CI: 1.516–2.853; p = 5.72 × 10−6).

Conclusion

This MR study found no causal effect of OSA on renal function in Europeans. However, genetically predicted increased BUN is associated with OSA development. These findings indicate that the relationship between OSA and renal function remains elusive and requires further investigation.
Association of systemic immune biomarkers with metabolic dysfunction-associated steatotic liver disease: a cross-sectional study of NHANES 2007–2018
Authors: Wang Yong , Chen Shude , Tian Chen , Wang Qi , Yang Zhihua , Che Wieqi , Li Yike , Luo Yang
Published: September 2024

Objective

Numerous studies emphasize the pivotal role of inflammation in metabolic dysfunction-associated steatotic liver disease (MASLD) development. Some link specific systemic immune biomarkers (e.g., systemic immuno-inflammatory index [SII], neutrophil-to-albumin ratio [NPAR] and neutrophil-to-lymphocyte ratio [NLR]) to hepatic steatosis risk. However, the relevance of other markers like systemic immune-inflammation index [SIRI], platelet-to-lymphocyte ratio [PLR] and lymphocyte/monocyte ratio [LMR] in MASLD remains unclear. Limited literature covers all six markers together. This study aims to investigate the association between SII, SIRI, LMR, NLR, PLR, and NPAR and MASLD, assessing their predictive value.

Methods

In this cross-sectional analysis of adults from NHANES (2007–2018), we investigated the relationship between six systemic immune biomarkers, stratified by quartiles: quartile1 (Q1), quartile2 (Q2), quartile3 (Q3) and quartile4 (Q4), and the outcome of MASLD assessed by Fatty Liver Index (FLI) and United States Fatty Liver Index (USFLI). Logistic regression and restricted cubic splines (RCS) were employed to assess the association between systemic immune biomarkers and MASLD risks. Propensity score matching controlled for potential confounders, and receiver operating characteristic (ROC) curve analysis evaluated the biomarkers’ predictive performances for MASLD. Subgroup and interaction analysis were conducted to explore the effects of systemic immune biomarkers on MASLD risks. Multicollinearity was quantified using the variance inflation factor.

Results

In total, 14,413 participants were included and 6,518 had MASLD. Compared with non-MASLD, participants with MASLD had higher SII, SIRI, NLR, PLR, and NPAR (p < 0.001). SII, SIRI, NLR, and NPAR were further validated in the restricted cubic splines (RCS) regression model and identified as positive linear relationships (p for nonlinear >0.05). The prevalence of MASLD increased with the Q4 of SII [OR = 1.47, 95%CI (1.24, 1.74)], SIRI [OR = 1.30, 95%CI (1.09, 1.54)], NLR [OR = 1.25, 95%CI (1.04, 1.49)], PLR [OR = 1.29, 95%CI (1.09, 1.53)] and NPAR [OR = 1.29, 95%CI (1.09, 1.54)] compared to the Q1 after adjusting for the bias caused by potential confounders. However, the propensity score matching analysis only supported an association between the highest SII, SIRI, NLR NPAR and the risk of MASLD. The results of the subgroup analysis showed considerable robustness in the relationship.

Conclusion

Higher SII, SIRI, NLR and NPAR were positively associated with a heightened risk of MASLD. NPAR showed the superior predictive value, followed by SII, SIRI and NLR. This needs to be validated in additional longitudinal studies and clinical trials.
Fish and meat intake in relation to colorectal adenoma in asymptomatic Korean adults
Authors: Kim Young Sun , Okekunle Akinkunmi Paul , Yang Sun Young , Song Ji Hyun , Youn Jiyoung , Kwon Gabby Yoon Jeong , Lee Jung Eun
Published: September 2024

Introduction

Colorectal adenomas are recognized as precursors to colorectal cancer through the adenoma-carcinoma sequence. Identifying modifiable dietary factors that may inhibit cancer progression is critical, but epidemiologic studies in Asian populations are scarce.

Methods

This study explored the impact of fish and meat intake on colorectal adenoma risk among Koreans. The study enrolled asymptomatic adults who visited Seoul National University Hospital Healthcare System Gangnam Center for health check-ups from May to December 2011. All participants underwent screening colonoscopy and completed a validated food frequency questionnaire. The study included 536 adenoma patients, 135 high-risk adenoma patients and 1,122 adenoma-free controls. Using multivariate logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for fish and meat intake related to colorectal adenoma status, significant at p < 0.05.

Results

The intake of total fish, meat, red meat, chicken or processed meat showed no clear association with the prevalence of colorectal adenoma after adjusting for age, education, smoking status, alcohol intake, physical activity, body mass index, metabolic syndrome, colorectal cancer family history, total energy intake, and total fruit and vegetable intake. However, higher fish intake was associated with lower odds of high-risk colorectal adenoma, with a significant trend observed across quartiles (P for trend = 0.04). This trend was more pronounced among men than women (P for trend = 0.01).

Conclusion

In conclusion, we observed a significant inverse association between high fish intake and the prevalence of high-risk adenoma, but there were no clear associations between red and processed meat or chicken in the Korean population.
A phase III study to access the safety and efficacy of prolgolimab 250 mg fixed dose administered every 3 weeks versus prolgolimab 1 mg/kg every 2 weeks in patients with metastatic melanoma (FLAT)
Authors: Demidov Lev , Kharkevich Galina , Petenko Natalia , Moiseenko Vladimir , Protsenko Svetlana , Semiglazova Tatiana , Zimina Anastasia , Kovalenko Nadezhda , Fadeeva Natalia , Kirtbaya Dmitry , Belogortsev Igor , Tantsyrev Denis , Odintsova Svetlana , Nesterova Alfia , Vorontsova Karina , Makarycheva Yulia , Linkova Yulia , Zinkina-Orikhan Arina , Siliutina Anna , Sorokina Irina , Liaptseva Daria , Chistyakov Vladimir , Lutsky Anton
Published: September 2024

Background

Prolgolimab is the first Russian PD-1 inhibitor approved for the first-line treatment of unresectable or metastatic melanoma and advanced non-small cell lung cancer. It was approved in two weight-based regimens of 1 mg/kg Q2W and 3 mg/kg Q3W, but because of re-evaluation of weight-based dosing paradigm, studying of a fixed-dose regimen was considered perspective.

Methods

We conducted a multicenter, single-arm, open-label efficacy, pharmacokinetics, and safety study to obtain data that would allow the approval of the new flat dosing regimen of prolgolimab in patients with previously untreated unresectable or metastatic melanoma (BCD-100-8/FLAT, NCT05783882). The primary objective was to prove the non-inferiority of prolgolimab 250 mg Q3W versus prolgolimab 1 mg/kg Q2W for the treatment of patients with unresectable or metastatic melanoma in terms of ORR according to RECIST 1.1. Patients from the MIRACULUM study (BCD-100-2/MIRACULUM, NCT03269565) comprised a historical control group.

Results

One hundred fourteen patients received prolgolimab 250 mg Q3W, and 61 patients received prolgolimab (Prolgo) 1 mg/kg Q2W (historical control). Objective response was achieved by 33.3% [95% confidence interval (CI): 24.8, 42.8] of patients in the Prolgo 250 mg group compared with 32.8% (95% CI: 21.3, 46.0) of patients in the Prolgo 1 mg/kg group. Risk difference was 0.00, 95% CI (−0.12; NA), p = 0.0082. Both regimens were well tolerated, and safety profiles were comparable. The pharmacokinetic analysis (PK) showed that the regimen with the fixed dose of 250 mg Q3W was characterized by higher PK parameters. The immunogenicity study did not detect binding antibodies to prolgolimab in any of the subjects.

Conclusion

The obtained results showed that the selected fixed dosing regimen of prolgolimab 250 mg Q3W is characterized by efficacy and safety parameters comparable to that observed for the 1 mg/kg Q2W regimen.
Weisheng-tang protects against ischemic brain injury by modulating microglia activation through the P2Y12 receptor
Authors: Kim Min Jae , Lee Dohee , Ryu Ji Hye , Lee Seo-Yeon , Choi Byung Tae , Yun Young Ju , Shin Hwa Kyoung
Published: September 2024

Background: Stroke, a leading cause of death and disability, lacks effective treatments. Post-stroke secondary damage worsens the brain microenvironment, further exacerbating brain injury. Microglia’s role in responding to stroke-induced damage in peri-infarct regions is crucial. In this study, we explored Weisheng-tang’s potential to enhance ischemic outcomes by targeting microglia.

Methods: We induced middle cerebral artery occlusion and reperfusion in mice, followed by behavioral assessments and infarct volume analyses after 48 h, and examined the changes in microglial morphology through skeleton analysis.

Results: Weisheng-tang (300 mg/kg) significantly reduced infarction volume and alleviated neurological and motor deficits. The number of activated microglia was markedly increased within the peri-infarct territory, which was significantly reversed by Weisheng-tang. Microglial morphology analysis revealed that microglial processes were retracted owing to ischemic damage but were restored in Weisheng-tang-treated mice. This restoration was accompanied by the expression of the purinergic P2Y12 receptor (P2Y12R), a key regulator of microglial process extension. Weisheng-tang increased neuronal Kv2.1 clusters while suppressing juxtaneuronal microglial activation. The P2Y12R inhibitor—ticagrelor—eliminated the tissue and functional recovery that had been observed with Weisheng-tang after ischemic damage.

Discussion: Weisheng-tang improved experimental stroke outcomes by modulating microglial morphology through P2Y12R, shedding light on its neuroprotective potential in ischemic stroke.
FTO diversely influences sensitivity of neuroblastoma cells to various chemotherapeutic drugs
Authors: Lin Meizhen , Hua Zhongyan , Li Zhijie
Published: September 2024

Chemotherapy resistance is a significant factor in treatment failure in patients with neuroblastoma (NB), and it directly affects patient prognosis. Therefore, identifying novel therapeutic targets to enhance chemosensitivity is essential to improve the cure rate and prognosis of patients with NB. In this study, we investigated the role of FTO in chemosensitivity of NB cells to various chemotherapeutic drugs. Our results showed that high FTO expression was positively correlated with increased survival probability and favorable prognostic factors in patients with NB. FTO overexpression inhibited cell proliferation, whereas FTO knockdown promoted cell proliferation in NB cells. FTO expression alteration had contrasting effects on NB cells’ sensitivity to etoposide but had no significant impact on sensitivity to cisplatin. Downregulation of FTO reduced the sensitivity of NB cells to paclitaxel, whereas upregulation of FTO enhanced its sensitivity. Additionally, the sensitivities between patients with lower and higher FTO expression to various chemotherapeutic drugs or small-molecule inhibitors were different. Thus, FTO affects the sensitivities of NB cells differently depending on the different chemotherapeutic drugs and small-molecule inhibitors. This finding may guide physicians and patients choose the appropriate chemotherapeutic drugs or small-molecule inhibitors for treatment.
The efficacy of stereotactic radiotherapy followed by bevacizumab and temozolomide in the treatment of recurrent glioblastoma: a case report
Authors: Zhong Wangyan , Mao Jiwei , Wu Dongping , Peng Jianghua , Ye Wanli
Published: September 2024

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor among adults. Despite advancements in multimodality therapy for GBM, the overall prognosis remains poor, with an extremely high risk of recurrence. Currently, there is no established consensus on the optimal treatment option for recurrent GBM, which may include reoperation, reirradiation, chemotherapy, or a combination of the above. Bevacizumab is considered a first-line treatment option for recurrent GBM, as is temozolomide. However, in recurrent GBM, it is necessary to balance the risks and benefits of reirradiation in combination with bevacizumab and temozolomide. Herein, we report the case of a patient with recurrent GBM after standard treatment who benefited from stereotactic radiotherapy followed by bevacizumab and temozolomide maintenance therapy. Following 16 months of concurrent chemoradiotherapy (CCRT), the patient was diagnosed with recurrent GBM by a 3-T contrast-enhanced magnetic resonance imaging (MRI). The addition of localized radiotherapy to the ongoing treatment regimen of bevacizumab, in combination with temozolomide therapy, prolonged the patient’s disease-free survival to over 2 years, achieving a significant long-term outcome, with no notable adverse effects observed. This clinical case may provide a promising new option for patients with recurrent GBM.
Cost-effectiveness analysis of first-line sintilimab plus chemotherapy vs. chemotherapy alone for unresectable advanced or metastatic gastric or gastroesophageal junction cancer in China
Authors: Xiang Zuojuan , Ma Ling , Fu Yingzhou , Pan Yong
Published: September 2024

Background

The Chinese Society of Clinical Oncology (CSCO) has recommended sintilimab plus chemotherapy (SINT + Chemo) as a standard first-line therapy for advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC), based on the proven effectiveness and safety in the ORINT-16 trail. Its cost-effectiveness, however, remains to be evaluated.

Methods

We established a partitioned survival approach (PartSA) model with a 10-year time horizon to determine whether SINT + Chemo (vs. chemotherapy) was more cost-effective as a first-line treatment for unresectable advanced or metastatic GC/GEJC. Survival data was generated from the ORIENT-16 trail. Cost calculation was limited to direct medical costs. Database of Hunan Public Resources Trading Service Platform was used as the source for obtaining drug prices. Other cost and utility values were gathered from established literature. Incremental cost-effectiveness ratio (ICER) was the primary output. Additionally, we conducted sensitivity analysis, subgroup analysis, and scenario analysis.

Results

In the base-case analysis, group SINT + Chemo showed an increase in utility value by 0.32 quality-adjusted life-years (QALYs) at an extra cost of $7988.43, resulting in an ICER of $25239.29/QALY, below the Chinese cost-effective willingness-to-pay (WTP) threshold of $38223.34. Upon further subgroup analysis according to patients’ programmed death 1 ligand (PD-L1) combined positive score (CPS), the ICERs were $26341.01/QALY for patients highly expressing PD-L1 (CPS ≥5) and $17658.26/QALY for patients lowly expressing PD-L1 (CPS <5). Based on the sensitivity analysis, we found the PFS utility was the parameter that had the most significant impact on the model’s outcomes. Moreover, in scenario analysis, the results remained consistent despite variations in the model’s time frame.

Conclusion

In China, SINT + Chemo is a more cost-effective option (vs. chemotherapy) as a first-line therapy for unresectable advanced or metastatic GC/GEJC, irrespective of PD-L1 expression levels.
The influence of modified Qing E Formula on the differential expression of serum exosomal miRNAs in postmenopausal osteoporosis patients
Authors: Lu Junjie , Wu Hui , Jin Huan , He Ziyi , Shen Lin , Ma Chen , Xu Xiaojuan , Wang Zixian , Shuai Bo
Published: September 2024

Objective

Although guidelines support the efficacy of Modified Qing’ E Formula (MQEF) in treating postmenopausal osteoporosis (PMOP), its underlying mechanisms remain incompletely understood. This retrospective investigation aims to elucidate MQEF’s impact on serum exosomal miRNA expression in postmenopausal osteoporosis patients and to explore potential therapeutic mechanisms.

Methods

Following ethical approval and registration, postmenopausal osteoporosis patients aged 50–85 years, meeting the diagnostic criteria were randomly selected and received MQEF decoction supplementary therapy. Serum samples were collected pre- and post-treatment, followed by isolation and sequencing of exosomal miRNAs. Differential miRNAs in serum exosomes were identified, and bioinformatics analysis was conducted to discern the principal exosomal miRNAs involved in MQEF’s effects on PMOP and the associated signaling pathways.

Results

Eighteen clinical blood samples were collected. A total of 282,185 target genes were detected across the three groups. 306 miRNAs exhibited altered expression in serum exosomes of PMOP patients, while MQEF intervention resulted in changes in 328 miRNAs. GO enrichment analysis revealed the immune and endocrine systems was pertained. KEGG enrichment analysis indicated associations between PMOP occurrence and MQEF treatment with cytokine interactions, oxidative phosphorylation, and the renin-angiotensin system. Intersectional analysis identified 17 miRNAs, including 2 consistent trends. miR-3188 as a potentially pivotal miRNA implicated in both PMOP occurrence and MQEF treatment.

Conclusion

This study constitutes the first randomized, retrospective clinical exploration confirming that MQEF demonstrates regulatory influence over exosomal miRNA expression in PMOP patients’ serum, its impact likely involves modulation of the immune and endocrine systems, as well as the renin-angiotensin system.
Chemometric analysis of monoterpenes and sesquiterpenes of conifers
Authors: Bakó Eszter , Böszörményi Andrea , Vargáné Szabó Bettina , Engh Marie Anne , Hegyi Péter , Ványolós Attila , Csupor Dezső
Published: September 2024

Volatile organic compounds (VOCs) and essential oils of conifers are widely used in the pharmaceutical industry. This work aimed to analyze the VOCs of 30 conifer species representing the Pinaceae and Cupressaceae families. Samples were collected from arboreta in Hungary, and their chemical composition was determined by gas chromatography (SPME-GC/MS); then, chemometric analyses were performed using multivariate methods to identify characteristic VOCs of conifers. Here, we present results for monoterpene and sesquiterpene profiles of the examined conifer samples. The most abundant compounds detected were α-pinene, bornyl acetate, limonene, β-pinene, β-caryophyllene, β-myrcene, δ-3-carene, and β-phellandrene. The results showed that the following volatiles were characteristic of the conifer groups: sabinene (RRT=6.0) for the cupressoid group (which includes the Cupressaceae species), longifolene (RRT=15.0) and β-pinene (RRT=6.1) were characteristic of the pinoid group (including Picea, Pinus, and Pseudotsuga species), and camphene (RRT=5.5) and bornyl acetate (RRT=12.6) were characteristic of the abietoid group (including Abies, Cedrus, and Tsuga species). Our results on VOCs in the Pinaceae and Cupressaceae families contribute to the elucidation of biodiversity patterns of conifer species and, in addition, may support the industrial application of terpenes.
Zinc oxide nanoparticles application alleviates salinity stress by modulating plant growth, biochemical attributes and nutrient homeostasis in Phaseolus vulgaris L
Authors: Gupta Aayushi , Bharati Rohit , Kubes Jan , Popelkova Daniela , Praus Lukas , Yang Xinghong , Severova Lucie , Skalicky Milan , Brestic Marian
Published: September 2024

Salt stress poses a significant challenge to global agriculture, adversely affecting crop yield and food production. The current study investigates the potential of Zinc Oxide (ZnO) nanoparticles (NPs) in mitigating salt stress in common beans. Salt-stressed bean plants were treated with varying concentrations of NPs (25 mg/L, 50 mg/L, 100 mg/L, 200 mg/L) using three different application methods: foliar application, nano priming, and soil application. Results indicated a pronounced impact of salinity stress on bean plants, evidenced by a reduction in fresh weight (24%), relative water content (27%), plant height (33%), chlorophyll content (37%), increased proline (over 100%), sodium accumulation, and antioxidant enzyme activity. Application of ZnO NPs reduced salt stress by promoting physiological growth parameters. The NPs facilitated enhanced plant growth and reduced reactive oxygen species (ROS) generation by regulating plant nutrient homeostasis and chlorophyll fluorescence activity. All the tested application methods effectively mitigate salt stress, with nano-priming emerging as the most effective approach, yielding results comparable to control plants for the tested parameters. This study provides the first evidence that ZnO NPs can effectively mitigate salt stress in bean plants, highlighting their potential to address salinity-induced growth inhibition in crops.
Effect of different vegetation restoration patterns on community structure and co-occurrence networks of soil fungi in the karst region
Authors: Zou Xiaoxiao , Yao Kai , Zeng Zhaoxia , Zeng Fuping , Lu Lihong , Zhang Hao
Published: September 2024

Introduction

The Grain for Green Project (GGP) by the Chinese government was an important vegetation restoration project in ecologically fragile and severely degraded karst regions. Soil fungi play a facilitating role in the cycling of nutrients both above and below the ground, which is crucial for maintaining ecosystem function and stability. In karst regions, their role is particularly critical due to the unique geological and soil characteristics, as they mitigate soil erosion, enhance soil fertility, and promote vegetation growth. However, little is known about how the implementation of this project shifts the co-occurrence network topological features and assembly processes of karst soil fungi, which limits our further understanding of karst vegetation restoration.

Methods

By using MiSeq high-throughput sequencing combined with null model analysis technology, we detected community diversity, composition, co-occurrence networks, and assembly mechanisms of soil fungi under three GGP patterns (crop, grassland, and plantation) in the southwestern karst region.

Results

Ascomycota and Basidiomycota were the main fungal phyla in all the karst soils. Returning crop to plantation and grassland had no significant effect on α diversity of soil fungi (P > 0.05), but did significantly affect the β diversity (P = 0.001). Soil moisture and total nitrogen (TN) were the main factors affecting the community structure of soil fungi. Compared with crop, soil fungi networks in grassland and plantation exhibited a higher nodes, edges, degree, and relatively larger network size, indicating that vegetation restoration enhanced fungal interactions. The soil fungi networks in grassland and plantation were more connected than those in crop, implying that the interaction between species was further strengthened after returning the crop to plantation and grassland. In addition, null-model analysis showed that the assembly process of soil fungal communities from crop to grassland and plantation shifted from an undominant process to dispersal limitation.

Discussion

These data indicated that GGP in karst region changed the composition and assembly mechanisms of the soil fungal community and enhanced the interaction between fungal species, which can contribute to a better understanding of the fungal mechanisms involved in the restoration of degraded karst soils through vegetation recovery.
Fine genetic mapping and transcriptomic analysis revealed major gene modulating the clear stripe margin pattern of watermelon peel
Authors: Yang Shao , Amanullah Sikandar , Duan Yaru , Guo Yu , Xu Ming , Bao Xiuping , An Bohan , Yuan Chengzhi , Liu Xiujie , Liu Jixiu , Gao Yue , Zhao Wen , Li Xinyuan , Gao Meiling
Published: September 2024

The peel stripe margin pattern is one of the most important quality traits of watermelon. In this study, two contrasted watermelon lines [slb line (P1) with a clear peel stripe margin pattern and GWAS-38 line (P2) with a blurred peel stripe margin pattern] were crossed, and biparental F2 mapping populations were developed. Genetic segregation analysis revealed that a single recessive gene is modulating the main-effect genetic locus (Clcsm) of the clear stripe margin pattern of peel. Bulked segregant analysis-based sequencing (BSA-Seq) and fine genetic mapping exposed the delimited Clcsm locus to a 19.686-kb interval on chromosome 6, and the Cla97C06G126680 gene encoding the MYB transcription factor family was identified. The gene mutation analysis showed that two non-synonymous single-nucleotide polymorphism (nsSNP) sites [Chr6:28438793 (A-T) and Chr6:28438845 (A-C)] contribute to the clear peel stripe margin pattern, and quantitative real-time polymerase chain reaction (qRT-PCR) also showed a higher expression trend in the slb line than in the GWAS-38 line. Further, comparative transcriptomic analysis identified major differentially expressed genes (DEGs) in three developmental periods [4, 12, and 20 days after pollination (DAP)] of both parental lines. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses indicated highly enriched DEGs involved in metabolic processes and catalytic activity. A total of 44 transcription factor families and candidate genes belonging to the ARR-B transcription factor family are believed to regulate the clear stripe margin trait of watermelon peel. The gene structure, sequence polymorphism, and expression trends depicted significant differences in the peel stripe margin pattern of both parental lines. The ClMYB36 gene showed a higher expression trend for regulating the clear peel stripe margin of the slb line, and the ClAPRR5 gene depicted a higher expression for modulating the blurred peel stripe margin in the GWAS-38 line. Overall, our fine genetic mapping and transcriptomic analysis revealed candidate genes differentiating the clear and blurred peel stripe patterns of watermelon fruit.