bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of perioperative thyrotoxicosis – what to do when standard therapy is contraindicated or fails?
Authors: Tian Kristy , Liang Trilene , Yew Jielin , Chng Chiaw-Ling
Published: December 2024

Background

Current guidelines recommend that hyperthyroid patients should be rendered euthyroid prior to surgical procedures. These guidelines rely heavily on the use of ATDs as the primary medication, and do not give recommendations for patients who have contraindications to ATDs, or for whom standalone ATD treatment is inadequate.

Objectives

To evaluate the efficacy and safety of adjunctive pharmacological therapy and/or therapeutic plasma exchange (TPE) in the perioperative management of patients with thyrotoxicosis who were intolerant to ATD or for whom standalone ATD therapy was inadequate to achieve euthyroidism prior to surgery.

Methods

A comprehensive search of MEDLINE, Google Scholar, Embase and CENTRAL up to 31 December 2023 retrieved 12,876 records. After screening titles, abstracts and full manuscripts, 16 reports were enrolled. The study quality was evaluated using the Newcastle-Ottawa Scale (NOS).

Results

Patients were primarily female (78.5%), aged between 35 and 52 years. The predominant thyroid condition was Graves’ disease (89.7%). Majority underwent thyroidectomy (99.3%). Patients treated pre-operatively with 2nd line pharmacotherapy with/without therapeutic plasma exchange (TPE) underwent surgery safely with no reports of perioperative thyroid storm. Pre-operative treatment achieved mean percentage reduction of free thyroxine and free triiodothyronine levels of 52.6 ± 8.2% and 68.1 ± 9.3% respectively. One study reported a patient who suffered from myocardial infarction and tachyarrhythmia and subsequently demised.

Conclusion

Preoperative management of hyperthyroidism with second line pharmacotherapy and/or TPE can be effectively and safely implemented in patients with intolerance to or ineffective treatment with ATDs. The treatment modalities were generally safe, though some complications were observed.
Does enterprise green innovation contribute to the carbon emission reduction? Evidence from China
Authors: Xie Jiajin , Wang Yindan
Published: December 2024

Green innovation serves as a driving force for enterprises to enhance their competitiveness and may offer an effective pathway for reducing carbon emissions. This study, using data on green innovation and carbon emissions from publicly listed companies between 2000 and 2022, examines the impact of green innovation on enterprise carbon emissions and its specific transmission channels. The findings reveal that: 1) Green innovation significantly reduces enterprise carbon emissions, and this inhibitory effect remains robust across a series of stability tests. 2) Mechanistically, green innovation primarily decreases carbon emissions through improvements in energy efficiency and the specialization of enterprise management. 3) Compared to the application for green utility model patents, green innovation through the application for green invention patents is more effective in reducing enterprise carbon emissions. The carbon emission reduction effect of green innovation is found to be more pronounced in non-state-owned enterprises compared to state-owned enterprises. Furthermore, when comparing the pollution intensity and technological complexity of industries, the suppressive effect of green innovation on carbon emissions is stronger for enterprises operating in highly polluting and technologically complex industries. The findings of this study provide empirical evidence to support the promotion of green innovation for facilitating the green and low-carbon transition of manufacturing enterprises in developing countries.
Predicting climate change impacts on distribution and conservation of critically endangered Picea neoveitchii using MaxEnt
Authors: Xue Ninghan , Li Kaiyuan , Chen Kexin , Li Panpan , Ji Xinmiao , Ma Zhilin , Ji Wenli
Published: December 2024

Picea neoveitchii Mast., an endemic and rare species in China, classified as Critically Endangered (CR) in the IUCN Red List of Threatened Species, possesses significant research value due to its unique biological characteristics that contribute to plant taxonomy and the conservation of the genus Picea. Despite its excellent timber quality and high ornamental value, it has not been widely used and well protected. This study employed the MaxEnt modeling approach, incorporating field survey data on species distribution and species distribution data collected online, along with climatic and environmental data sourced from IPCC reports and climate databases. It assessed the current and future distribution ranges, influential variables, and conservation status of P. neoveitchii. The results indicate that Minimum Temperature of the Coldest Month, Annual Precipitation, Temperature Seasonality, and Altitude are the key factors influencing the distribution of P. neoveitchii. Across all future climate scenarios, the suitable habitat for P. neoveitchii consistently exhibits a trend of shifting northwestwards. Under SSP2-4.5, SSP5-5.8 scenario, the suitable area decreases in all periods. Under SSP1-2.6 scenario, the suitable area decreases, except the period from 2080 to 2,100, which sightly increases. Notably, the proportion of habitat within natural reserves increased. To conserve P. neoveitchii, it is necessary to adopt in-situ and ex-situ conservation measures, conserve germplasm resources through seed banking and tissue culture, and implement strict enclosure policies to minimize human disturbance and promote natural regeneration. These findings highlight the need for targeted conservation measures to address the ongoing threat to this species.
The complete chloroplast genome of Illicium verum and comparative analysis with related species from Magnoliaceae and Illiciaceae
Authors: Cao Yingying , Lai Yongxing , Li Zhuxin , Zhai Shanshan , Dai Yinghan , Tao Junyu , Wang Qing , Xu Ziheng , Jiang Minjie , Yu Li , Leng Jing , Tang Haibo
Published: December 2024

Illicium verum (Illiciaceae), an ecologically significant endemic plant, predominantly grows in Guangxi, China, which is the primary region for its cultivation. This area accounts for more than 80% of the total cultivation and yield in China. Despite its importance, comprehensive studies on the chloroplast (cp) genome of I. verum are limited. In our research, we sequenced and analyzed the complete cp genome of I. verum and conducted a comparative analysis with nine related species from the families Magnoliaceae, Schisandraceae, and Illiciaceae. The cp genome of I. verum spans 143,187 base pairs (bp), comprising a large single copy (LSC) region of 100,868 bp, a small single copy (SSC) region of 20,235 bp, and two inverted repeats (IR) regions, each 11,042 bp in length. We identified 81 simple sequence repeats (SSRs) within this genome. The chloroplast genome contains 78 protein-coding genes, 8 ribosomal RNA (rRNA) genes, and 35 transfer RNA (tRNA) genes. Structurally, the IR regions exhibit greater similarity across different genera of Magnoliaceae and Illiciaceae compared to the LSC and SSC regions. Phylogenetic analysis revealed high homology between the cp genome of I. verum and those of Illicium burmanicum, Illicium simonsii, and Illicium anisatum. These findings suggest that the cp genome of I. verum may serve as a valuable genomic resource for elucidating the phylogenetic positions and relationships within the Illiciaceae family. This information will be instrumental for future taxonomic research on Illicium species and for advancing genomic studies of these plants.
Understanding how population change is associated with community sociodemographics and economic outcomes across the United States
Authors: Buresch Jasmina M. , Medgyesi Danielle , Porter Jeremy R. , Hirsch Zachary M.
Published: December 2024

This study examines how population change is associated with changes in sociodemographics and economic outcomes across diverse geographic contexts in the United States from 2000 to 2020. Using Census Tract-level data and generalized additive models (GAMs), we found that communities experiencing population growth showed significant improvements in socioeconomic indicators: for example, a 50% population increase in Northeast metropolitan non-coastal areas was associated with a $10,062 rise [95% confidence interval (CI) = $9,181, $10,944] in median household income. Conversely, areas with population decline faced increasing challenges to community composition: communities experiencing a 50% population decline in West coastal metropolitan areas saw their median age increase by 2.556 years (95% CI = 2.23, 2.89 years), indicating an accelerated aging population. We observed a positive relationship between population growth and local economic growth, with areas experiencing population decline or slow growth showing below-average economic growth. While population change alone explained 10.1% of the variance in county-level GDP growth, incorporating sociodemographic shifts alongside population change using a partial least squares regression (PLSR) more than doubled the explanatory power to 21.4%. Overall, we often found the strength of relationships and sometimes the direction varied by geographic context: coastal areas showed distinct patterns from inland regions, and metropolitan areas responded differently than rural ones. For instance, the percentage of owner-occupied housing was negatively associated with population growth in metropolitan areas, but positively associated in non-metropolitan areas. Our research provides valuable insights for policymakers and planners working to address community changes, particularly in the context of anticipated climate-induced migration. The results suggest that strategies for maintaining economic vitality need to consider not just population retention, but also demographic profiles and socioeconomic opportunities across different geographic contexts.
Integration of bulk/scRNA-seq and multiple machine learning algorithms identifies PIM1 as a biomarker associated with cuproptosis and ferroptosis in abdominal aortic aneurysm
Authors: Han Zonglin , Lu Xiulian , He Yuxiang , Zhang Tangshan , Zhou Zhengtong , Zhang Jingyong , Zhou Hua
Published: December 2024

Background

Abdominal aortic aneurysm (AAA) is a serious life-threatening vascular disease, and its ferroptosis/cuproptosis markers have not yet been characterized. This study was aiming to identify markers associated with ferroptosis/cuproptosis in AAA by bioinformatics analysis combined with machine learning models and to perform experimental validation.

Methods

This study used three scRNA-seq datasets from different mouse models and a human PBMC bulk RNA-seq dataset. Candidate genes were identified by integrated analysis of scRNA-seq, cell communication analysis, monocle pseudo-time analysis, and hdWGCNA analysis. Four machine learning algorithms, LASSO, REF, RF and SVM, were used to construct a prediction model for the PBMC dataset, the above results were comprehensively analyzed, and the targets were confirmed by RT-qPCR.

Results

scRNA-seq analysis showed Mo/MF as the most sensitive cell type to AAA, and 34 cuproptosis associated ferroptosis genes were obtained. Pseudo-time series analysis, hdWGCNA and machine learning prediction model construction were performed on these genes. Subsequent comparison of the above results showed that only PIM1 appeared in all algorithms. RT-qPCR and western blot results were consistent with sequencing results, showing that PIM1 was significantly upregulated in AAA.

Conclusion

In a conclusion, PIM1 as a novel biomarker associated with cuproptosis/ferroptosis in AAA was highlighted.
TLS and immune cell profiling: immunomodulatory effects of immunochemotherapy on tumor microenvironment in resectable stage III NSCLC
Authors: Yang Chaopin , You Jinqi , Wang Yizhi , Chen Si , Tang Yan , Chen Hao , Zhong Haoran , Song Ruyue , Long Hao , Xiang Tong , Zhao Ze-Rui , Xia Jianchuan
Published: December 2024

Background

The use of programmed death-1 (PD-1) inhibitors in the neoadjuvant setting for patients with resectable stage III NSCLC has revolutionized this field in recent years. However, there is still 40%-60% of patients do not benefit from this approach. The complex interactions between immune cell subtypes and tertiary lymphoid structures (TLSs) within the tumor microenvironment (TME) may influence prognosis and the response to immunochemotherapy. This study aims to assess the relationship between immune cells subtypes and TLSs to better understand their impact on immunotherapy response.

Methods

This study initially compared the tertiary lymphoid structures (TLSs) density among patients who underwent immunochemotherapy, chemotherapy and upfront surgery using 123 tumor samples from stage-matched patients. Multiplex immunohistochemistry (mIHC) was employed to analyze the spatial distribution of PD-L1+CD11c+ cells and PD1+CD8+ T cells within TLSs. Cytometry by time-of-flight (CyTOF) was used to assess immune cell dynamics in paired biopsy and resection specimens from six patients who underwent immunochemotherapy. Key immune cells were validated in newly collected samples using flow cytometry, mIHC, and in vitro CAR-T cells model.

Results

Patients who underwent neoadjuvant chemotherapy or immunochemotherapy exhibited increased TLSs compared to those who opted for upfront surgery. The TLS area-to-tumor area ratio distinguished pCR+MPR and NR patients in the immunochemotherapy group. Spatial analysis revealed variations in the distance between PD-L1+CD11c+ cells and PD1+CD8+ T cells within TLSs in the immunochemotherapy group. CyTOF analysis revealed an increase in the frequency of key immune cells (CCR7+CD127+CD69+CD4+ and CD38+CD8+ cells) following combined therapy. Treatment responders exhibited an increase in CCR7+CD4+ T cells, whereas CD38+CD8+ T cells were associated with compromised treatment effectiveness.

Conclusions

Immunochemotherapy and chemotherapy increase TLSs and granzyme B+ CD8+ T cells in tumors. The TLS area-to-tumor ratio distinguishes responders from non-responders, with PD-L1+ dendritic cells near CD8+PD-1+ T cells linked to efficacy, suggesting that PD-1 inhibitors disrupt harmful interactions. Post-immunochemotherapy, CD8+ T cells increase, but CD38+CD8+ T cells show reduced functionality. These findings highlight the complex immune dynamics and their implications for NSCLC treatment.
Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features
Authors: Boissière-Michot Florence , Chateau Marie-Christine , Thézenas Simon , Lafont Virginie , Crapez Evelyne , Sharma Priyanka , Bobrie Angélique , Roger Pascal , Guiu Séverine , Jacot William
Published: December 2024

Background

In triple-negative breast cancer (TNBC), the most immunogenic breast cancer type, tumor-infiltrating lymphocytes (TILs) are an independent prognostic factor. Tertiary lymphoid structures (TLS) are an important TILs source, but they are not integrated in the current prognostic criteria.

Methods

In this retrospective study, TLS were assessed in hematein-eosin-saffron-stained (HES) histological sections from 397 early, chemotherapy-naive TNBC samples after primary surgical resection. Their association with i) classical clinicopathological features, ii) TILs and CD3+, CD8+, CD20+ lymphoid populations, iii) CD68+, CD163+, CD11b+, CD66b+ myeloid populations, and iv) expression of the PD1/PD-L1 and PVR/TIGIT axis immune checkpoint components and their prognostic significance were evaluated.

Results

TLS were observed in 88.2% of samples, mainly in peritumoral areas (86.1%). Increased amount of peritumoral TLS (PT-TLS) was significantly associated with younger age (p<0.001), smaller tumor size and higher tumor grade (both, p<0.001), HER2null tumors (versus HER2low tumors, p<0.002), and non-lobular histological type (p<0.016). TNBC with higher PT-TLS abundance displayed more often a basal-like (p<0.001) and not molecular-apocrine phenotype (p<0.001). TLS abundance was associated with TILs and hot tumor inflammatory pattern (both, p<0.001). Remarkably, PT-TLS abundance was positively associated with the density of the analyzed lymphoid (CD3+, CD8+, CD20+) and myeloid (CD68+, CD163+, CD11b+) cell populations (all p<0.001), with the exception of CD66b+ cells, as well as with expression of the PD1/PD-L1 and TIGIT/PVR immune checkpoint markers. In univariate analysis, beside the classical clinicopathological factors (tumor size, node involvement and adjuvant chemotherapy), TILs, hot tumors and PT-TLS were significantly associated with clinical outcome. Moreover, the risk of relapse was inversely correlated with PT-TLS abundance (Kaplan-Meier analysis). In multivariate analysis, pathological stage, adjuvant chemotherapy and PT-TLS remained correlated with relapse-free survival.

Conclusion

Our results suggest that TLS are a frequent feature in early TNBC and that their presence, particularly at the tumor periphery, recapitulates the tumor immune microenvironment. In our series, their prognostic value outperformed that of TILs. Therefore, their easy quantification on routine HES sections and their integration into the factors classically analyzed by pathologists could improve the clinical management of TNBC, a breast cancer type whose prognosis remains too poor.
Metabolism and immune responses of striped hamsters to ectoparasite challenges: insights from transcriptomic analysis
Authors: Lun Xinchang , Wang Yiguan , Zhao Ning , Yue Yujuan , Meng Fengxia , Liu Qiyong , Song Xiuping , Liang Ying , Lu Liang
Published: December 2024

Introduction

The striped hamster, often parasitized by ectoparasites in nature, is an ideal model for studying host-ectoparasite molecular interactions. Investigating the response to ectoparasites under laboratory conditions helps elucidate the mechanism of host adaptations to ectoparasite pressure.

Methods

Using transcriptome sequencing, we analyzed gene expression in striped hamsters after short-term (3 days) and long-term (28 days) flea (Xenopsylla cheopis) parasitism. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hub genes were pinpointed using protein-protein interaction (PPI) network analysis and the MCODE in Cytoscape. Gene Set Enrichment Analysis (GSEA) was used to further clarify the functional pathways of these hub genes. Validation of DEGs was performed via RT-qPCR. Additionally, the concentrations of reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined using specific enzyme-linked immunosorbent assay (ELISA) detection kits for hamsters.

Results

GO analysis revealed that during early parasitism, hosts primarily responded to the ectoparasites by adjusting the expression of genes related to metabolic functions. As parasitism persisted, the immune response became prominent, activating various immune pathways against ectoparasites. KEGG analysis confirmed the ongoing roles of metabolism and immunity. Notably, the chemical carcinogenesis - reactive oxygen species pathway was upregulated during flea parasitism, with downregulation of hub genes ATP5MC1 and ATP5MC2, highlighting the importance of mitochondrial function in oxidative stress. ELISA findings revealed that on day 3, flea parasitism groups showed elevated ROS expression and reduced SOD and CAT levels compared to the control group. By day 28, only SOD expression showed a significant decrease in both parasitism groups.

Conclusion

This study uncovered the dynamic changes in metabolism and immune responses of striped hamsters parasitized by Xenopsylla cheopis. Hosts adjust their physiological and immune states to optimize survival strategies during different ectoparasite stages, enhancing our understanding of host-ectoparasite interactions. This also paves the way for further research into how hosts regulate complex biological processes in response to ectoparasite challenges.
The 'genetic zipper' method offers a cost-effective solution for aphid control
Authors: Oberemok Vol V. , Puzanova Yelizaveta V. , Gal’chinsky Nikita V.
Published: December 2024

Twenty years ago, it was difficult to imagine the use of nucleic acids in plant protection as insecticides, but today it is a reality. New technologies often work inefficiently and are very expensive; however, qualitative changes occur during their development, making them more accessible and work effectively. Invented in 2008, contact oligonucleotide insecticides (olinscides, or DNA insecticides) based on the CUAD (contact unmodified antisense DNA) platform have been substantially improved and rethought. The main paradigm shift was demonstrating that unmodified antisense DNA can act as a contact insecticide. Key breakthroughs included identifying convenient target genes (rRNA genes), mechanism of action (DNA containment), and discovering insect pests (sternorrhynchans) with high susceptibility to olinscides. Today, the CUAD platform possesses impressive characteristics: low carbon footprint, high safety for non-target organisms, rapid biodegradability, and avoidance of target-site resistance. This next-generation class of insecticides creates opportunities for developing products tailored for specific insect pest populations. The ‘genetic zipper’ method, based on CUAD biotechnology, integrates molecular genetics, bioinformatics, and in vitro nucleic acid synthesis. It serves as a simple and flexible tool for DNA-programmable plant protection using unmodified antisense oligonucleotides targeting pest rRNAs. Aphids, key pests of important agricultural crops, can be effectively controlled by oligonucleotide insecticides at an affordable price, ensuring efficient control with minimal environmental risks. In this article, a low-dose concentration (0.1 ng/µL; 20 mg per hectare in 200 L of water) of the 11 nt long oligonucleotide insecticide Schip-11 shows effectiveness against the aphid Schizolachnus pineti, causing mortality rate of 76.06 ± 7.68 on the 12th day (p<0.05). At a consumption rate of 200 L per hectare, the cost of the required oligonucleotide insecticide is about 0.5 USD/ha using liquid-phase DNA synthesis making them competitive in the market and very affordable for lab investigations. We also show that non-canonical base pairing Golinscide: UrRNA is well tolerated in aphids. Thus, non-canonical base-pairing should be considered not to harm non-target organisms and can be easily solved during the design of oligonucleotide insecticides. The ‘genetic zipper’ method, based on CUAD biotechnology, helps quickly create a plethora of efficient oligonucleotide pesticides against aphids and other pests. Already today, according to our estimations, the ‘genetic zipper’ is potentially capable of effectively controlling 10-15% of all insect pests using a simple and flexible algorithm.
Effect of alternating salinity stress on the gut microbiota of razor clam Sinonovacula constricta
Authors: Yuan Yi , Jiang Qunqun , Xue Qinggang , Lin Zhihua , Dai Wenfang
Published: December 2024

Introduction

Razor clam (Sinonovacula constricta) is a bivalve of economic importance that widely resides in coastal and estuarine areas where salinity fluctuates rapidly. Gut microbiota, which plays a pivotal role in the disease resistance against pathogens and the growth and development of aquatic animals, is affected by salinityfluctuation in ambient environment. However, there is limited knowledge about the underlying mechanism of how clam gut microbiota respond to alternating salinity stress.

Methods

Here, we exposed S. constricta to different salinity treatments including normal salinity-acclimated (NN, 20 psu), low salinity-acclimated (LL, 5 psu), low salinity-stressed (NL, transferred from 20 to 5 psu) and normal salinity-stressed (LN, transferred from 5 to 20 psu) groups. The former two groups were used as the control, and the latter two groups aimed to investigate the effect of alternating salinity stress on clam growth and gut microbiota by 16S rRNA gene amplicon sequencing.

Results

Alternating salinity stress caused faster and higher mortality compared with the two control groups, and disrupted the gut microbiota including altered α-diversity, composition and structure. The salinity stress, hours post stress and their interaction had significant impact on the gut microbiota, which contributed 4.5%, 9.5% and 6.0%, respectively, to the variance in the gut communities. Alternating salinity stress increased the proportion of stochastic processes in governing the gut microbiota to a certain extent, and the stochasticity aggravated with the increase of stress time. Furthermore, the gut bacterial interspecies interaction networks exhibited more complex and higher connected topology in two alternating salinity stress groups compared with the control group (NN), and the interaction relationships between core OTUs in gut networks were altered after salinity stress. The functional potentials involved in immune system and metabolisms of amino acid, energy, carbohydrate and lipid remarkably increased in LN and NN groups after salinity exposure for 96 h compared to corresponding 0 h, while these pathways exhibited the opposite pattern in NL and LL groups.

Discussion

Collectively, our findings provide evidence that alternating salinity stress has potentially negative effect on the growth of S. constricta from an ecological viewpoint.
Hand grip strength and all-cause mortality risk in individuals with decreased bone mass: a study from NHANES database
Authors: Sun Hongdong , Liu Jiayi , Tan Ruirui , Zhang Xiaomei , Qian Xin , Qi Chenxi , Qi Wei
Published: December 2024

Objective

Previous studies have demonstrated that grip strength is associated with various health outcomes, including osteoporosis. However, the impact of grip strength on long-term mortality risk among individuals with low bone mass remains unclear. This study aims to investigate the association between grip strength and the risk of all-cause mortality in the population with low bone mass.

Methods

We included 1,343 cases of decreased bone mass from the NHANES database spanning 2013 to 2014. All-cause mortality data were ascertained through linkage with national death index records up to December 31, 2015. Analysis was conducted using the Cox proportional hazards regression model, and we assessed result reliability through various model adjustments and hierarchical analyses, Schoenfeld’s global and individual tests are utilized to estimate the time-varying covariance in the Cox proportional hazards regression model’s hypothesis.

Results

Throughout an average follow-up period of 69.5 months, 148 deaths were documented. After adjusting for covariates, a significant association between grip strength and the risk of all-cause mortality was observed in individuals with decreased bone mass (HR = 0.9, 95% CI: 0.87–0.93, p < 0.001). Individuals with normal grip strength, compared to those with low grip strength, exhibited a 56% lower risk of all-cause mortality (HR = 0.44, 95% CI: 0.29–0.67, p < 0.001). Various models consistently demonstrated similar significant trends post-adjustment. Subgroup analysis revealed an interaction between grip strength and coronary heart disease (p < 0.05). Schoenfeld’s global and individual tests confirmed the reliability of the model (p > 0.05).

Conclusion

Our findings indicate that low grip strength is associated with increased all-cause mortality risk in individuals with decreased bone mass. The inclusion of routine monitoring of grip strength in patients with osteopenia and the encouragement of maintaining or improving grip strength in this population may offer a novel approach to health management for these individuals.
Research on the mechanism of core acupoints in electroacupuncture for functional constipation based on data mining and network acupuncture
Authors: Ong Shun Seng , Tang Ting , Xu Lianjie , Xu Canwei , Li Qi , Deng Xiaoyue , Shen Peihua , Chen Yi , Song Yang , Lu Hai , Fang Ling
Published: December 2024

Aim

Functional Constipation (FC) is a common gastrointestinal disorder that imposes a considerable strain on global health. It negatively impacts the quality of life and results in significant healthcare expenditures. Current treatments, such as lifestyle changes and medications, fail to meet patient satisfaction due to efficacy and safety issues. Electroacupuncture (EA), with its precise stimulation control and standardized protocols, shows promise in FC management. However, optimal EA parameters for FC treatment are yet to be established. Our study reviews EA applications in FC to inform a standardized treatment approach and explore EA’s therapeutic mechanisms.

Methods

This comprehensive study utilized research literature from databases including PubMed, Embase, OVID, Web of Science, the Cochrane Library, CNKI, VIP, and Wanfang to perform a descriptive analysis of acupoint selection and EA parameters. It proceeded to analyze high-frequency acupoint groupings and stimulus parameters, followed by the excavation and analysis of core acupoint prescriptions. Subsequent steps integrated potential target identification for these core formulas, the assembly of a “core acupoint-prescription-target-constipation” network, and the construction of a protein–protein interaction (PPI) network to extract central targets. Additionally, Gene Ontology (GO) and KEGG enrichment analyses were conducted to prognosticate the underlying mechanisms by which EA may exert its therapeutic effects on FC.

Results

In our study, we analyzed 141EA prescriptions for FC and identified a core set of acupoints including Tianshu (ST25), Fujie (SP14), Shangjuxu (ST37), and Zusanli (ST36) through data mining. The frequency of use was highest for Tianshu (ST25) with 119 occurrences, followed by Fujie (SP14) with 59, Shangjuxu (ST37) with 42, and Zusanli (ST36) with 23. PPI network analysis revealed key targets such as NFKB1, IL6, MyD88, TLR4, TNF, TLR2, and IL1B. GO and KEGG analyses of 49 constipation-associated targets identified 257 BP, 37 CC, and 41 MF terms, and 154 significant pathways, with the top 20 visualized for further analysis.

Conclusion

The core acupoint prescription of EA for FC can exert its therapeutic effects by acting on multiple targets and pathways synergistically especially on NFKB1, IL6, MyD88, TLR4, TNF, TLR2, and IL1B. The research findings have preliminarily validated the fundamental effects and related mechanisms of EA parameters and core prescriptions, providing direction for further in-depth exploration of the mechanisms of action.
PCSK9 inhibitor alleviates experimental pulmonary fibrosis-induced pulmonary hypertension via attenuating epithelial-mesenchymal transition by suppressing Wnt/β-catenin signaling in vivo and in vitro
Authors: Lin Jiancheng , Pan Zetao , Sun Jiayan , Wang Xiaowan , Yin Di , Huo Cunyang , Guo Qiang
Published: December 2024

Background

The co-occurrence of pulmonary hypertension (PH) in patients with pulmonary fibrosis (PF) is linked to a more unfavorable prognosis and increased mortality compared to PF cases without PH. Early intervention and comprehensive management are pivotal for improving survival outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein essential in cholesterol metabolism. However, the potential for PCSK9 inhibition to alleviate PF-induced PH has not been previously reported.

Methods

A mouse model of PF-induced PH was established using intratracheal injection of bleomycin (BLM), followed by administration of a PCSK9 inhibitor every other day. Data on right ventricle (RV) remodeling and changes in pulmonary arteries were collected and analyzed. Transforming growth factor-beta (TGF-β) was also administered to MLE-12 cells as an experimental lung fibrosis model. The mechanisms of PCSK9’s impact on lung fibrosis were examined both in vivo and in vitro.

Results

Inhibition of PCSK9 significantly reduced pulmonary artery thickening and RV remodeling in the BLM-induced mouse model. Moreover, the blockage of PCSK9 effectively attenuated the migration and epithelial-mesenchymal transition (EMT) process of TGF-β-induced MLE-12 cells. We also observed that the PCSK9 inhibitor suppressed the expression of the Wnt/β-catenin pathway in both animal and cell experiments.

Conclusion

PCSK9 plays a crucial role in the progression of PF-induced PH by regulating cell EMT and Wnt/β-catenin signaling. Targeting PCSK9 expression or activity could effectively control lung fibrosis and its PH complication.
Possible biocontrol of bacterial blight in pomegranate using native endophytic Bacillus spp. under field conditions
Authors: Manjunatha N. , Pokhare Somnath S. , Agarrwal Ruchi , Singh Nripendra V. , Sharma Jyotsana , Harsur Mallikarjun M. , Marathe Rajiv A.
Published: December 2024

Bacterial blight in pomegranate, caused by Xanthomonas citri pv. punicae (Xcp), is one of the most devastating diseases, leading to substantial economic losses in pomegranate production. Methods for blight management in pomegranate production are scarce and not well established. To date, the major control strategy is targeting the pathogen with antibiotics and copper-based compounds. However, excessive use of antibiotics has resulted in the development of antibiotic resistance in the field population of Xcp. Hence, as a means of eco-friendly and sustainable management of bacterial blight, the use of native endophytes was investigated under field conditions in the current study. Endophytic bacteria were isolated from micro-propagated nodal explants of pomegranate and were identified as Bacillus haynesii, B. tequilensis, and B. subtilis. They were found to produce volatiles that inhibited Xcp growth during in vitro antibiosis assay. GC–MS-based volatile profiling revealed the presence of several bioactive compounds with reported antimicrobial activities. These endophytes (CFU of 108/mL) were then spray-inoculated on leaves of 6-month-old pomegranate plants in the polyhouse. They were found to induce ROS-scavenging enzymes such as catalase and peroxidase. This alteration was a manifestation of host tissue colonization by the endophytes as ROS scavenging is one of the mechanisms by which endophytes colonize the host plants. Furthermore, two-season field trials with endophytes for blight control resulted in a reduction of disease index by 47–68%, which was considerably higher than the reduction due to the chemical immune modulator (2-bromo-2-nitro-1, 3-propanediol) currently being recommended for blight control. In addition, these endophytes also exhibited reduced sensitivity to this immune modulator; thus, the current study advocates the use of B. haynesii, B. subtilis, and B. tequilensis as biocontrol agents for bacterial blight of pomegranate either alone or as a part of integrated disease management.
Bacteroides thetaiotaomicron enhances oxidative stress tolerance through rhamnose-dependent mechanisms
Authors: Xie Shuo , Ma Junze , Lu Zheng
Published: December 2024

This study probes into the unique metabolic responses of Bacteroides thetaiotaomicron (B. thetaiotaomicron), a key player in the gut microbiota, when it metabolizes rhamnose rather than typical carbohydrates. Known for its predominant role in the Bacteroidetes phylum, B. thetaiotaomicron efficiently breaks down poly- and mono-saccharides into beneficial short-chain fatty acids (SCFAs), crucial for both host health and microbial ecology balance. Our research focused on how this bacterium’s SCFA production differ when utilizing various monosaccharides, with an emphasis on the oxidative stress responses triggered by rhamnose consumption. Notably, rhamnose use results in unique metabolic byproducts, including substantial quantities of 1,2-propanediol, which differs significantly from those produced during glucose metabolism. Our research reveals that rhamnose consumption is associated with a reduction in reactive oxygen species (ROS), signifying improved resistance to oxidative stress compared to other sugars. This effect is attributed to specific gene expressions within the rhamnose metabolic pathway. Notably, overexpression of the rhamnose metabolism regulator RhaR in B. thetaiotaomicron enhances its survival in oxygen-rich conditions by reducing hydrogen peroxide production. This reduction is linked to decreased expression of pyruvate:ferredoxin oxidoreductase (PFOR). In contrast, experiments with a rhaR-deficient strain demonstrated that the absence of RhaR causes B. thetaiotaomicron cells growing on rhamnose to produce ROS at rates comparable to cells grown on glucose, therefore, losing their advantage in oxidative resistance. Concurrently, the expression of PFOR is no longer suppressed. These results indicate that when B. thetaiotaomicron is cultured in a rhamnose-based medium, RhaR can restrain the expression of PFOR. Although PFOR is not a primary contributor to intracellular ROS production, its sufficient inhibition does reduce ROS levels to certain extent, consequently improving the bacterium’s resistance to oxidative stress. It highlights the metabolic flexibility and robustness of microbes in handling diverse metabolic challenges and oxidative stress in gut niches through the consumption of alternative carbohydrates.
An efficient co-culture of Halomonas mongoliensis and Dunaliella salina for phenol degradation under high salt conditions
Authors: Wang Changjian , Guo Haiqiao , Yu Peng , Huang Bo , Xin Zhikun , Zheng Xufan , Zhang Jinli , Tang Tao
Published: December 2024

Phenol is one of the major organic pollutants in high salt industrial wastewater. The biological treatment method is considered to be a cost-effective and eco-friendly method, in which the co-culture of microalgae and bacteria shows a number of advantages. In the previous study, a co-culture system featuring Dunaliella salina (D. salina) and Halomonas mongoliensis (H. mongoliensis) was established and could degrade 400 mg L−1 phenol at 3% NaCl concentration. In order to enhance the performance of this system, D. salina strain was subjected to adaptive laboratory evolution (ALE) by gradually increasing the phenol concentration from 200 mg L−1 to 500 mg L−1 at 3% NaCl concentration. At a phenol concentration of 500 mg L−1, the phenol removal rate of the resulting D. salina was 78.4% within 7 days, while that of the original strain was only 49.2%. The SOD, POD, and MDA contents of the resulting strain were lower than those of the original strain, indicating that the high concentration of phenol was less harmful to the resulting strain. A co-culture system was established with the resulting D. salina and H. mongoliensis, which could complete degrade 500 mg L−1 of phenol within 8 days, outperforming the original D. salina co-culture system. This study proved that ALE could improve the phenol tolerance and phenol degradation capability of D. salina, and then effectively improve the phenol degradation capability of D. salina and H. mongoliensis co-culture system.
Single-cell synaptome mapping: its technical basis and applications in critical period plasticity research
Authors: Uchigashima Motokazu , Mikuni Takayasu
Published: December 2024

Our brain adapts to the environment by optimizing its function through experience-dependent cortical plasticity. This plasticity is transiently enhanced during a developmental stage, known as the “critical period,” and subsequently maintained at lower levels throughout adulthood. Thus, understanding the mechanism underlying critical period plasticity is crucial for improving brain adaptability across the lifespan. Critical period plasticity relies on activity-dependent circuit remodeling through anatomical and functional changes at individual synapses. However, it remains challenging to identify the molecular signatures of synapses responsible for critical period plasticity and to understand how these plasticity-related synapses are spatiotemporally organized within a neuron. Recent advances in genetic tools and genome editing methodologies have enabled single-cell endogenous protein labeling in the brain, allowing for comprehensive molecular profiling of individual synapses within a neuron, namely “single-cell synaptome mapping.” This promising approach can facilitate insights into the spatiotemporal organization of synapses that are sparse yet functionally important within single neurons. In this review, we introduce the basics of single-cell synaptome mapping and discuss its methodologies and applications to investigate the synaptic and cellular mechanisms underlying circuit remodeling during the critical period.
Learning dynamic cognitive map with autonomous navigation
Authors: de Tinguy Daria , Verbelen Tim , Dhoedt Bart
Published: December 2024

Inspired by animal navigation strategies, we introduce a novel computational model to navigate and map a space rooted in biologically inspired principles. Animals exhibit extraordinary navigation prowess, harnessing memory, imagination, and strategic decision-making to traverse complex and aliased environments adeptly. Our model aims to replicate these capabilities by incorporating a dynamically expanding cognitive map over predicted poses within an active inference framework, enhancing our agent's generative model plasticity to novelty and environmental changes. Through structure learning and active inference navigation, our model demonstrates efficient exploration and exploitation, dynamically expanding its model capacity in response to anticipated novel un-visited locations and updating the map given new evidence contradicting previous beliefs. Comparative analyses in mini-grid environments with the clone-structured cognitive graph model (CSCG), which shares similar objectives, highlight our model's ability to rapidly learn environmental structures within a single episode, with minimal navigation overlap. Our model achieves this without prior knowledge of observation and world dimensions, underscoring its robustness and efficacy in navigating intricate environments.
Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot study
Authors: Otzel Dana M. , Nichols Larissa , Conover Christine F. , Marangi Stephen A. , Kura Jayachandra R. , Iannaccone Dominic K. , Clark David J. , Gregory Chris M. , Sonntag Christopher F. , Wokhlu Anita , Ghayee Hans K. , McPhaul Michael J. , Levy Charles E. , Plumlee Charles A. , Sammel Robert B. , White Kevin T. , Yarrow Joshua F.
Published: December 2024

Background

High-dose testosterone replacement therapy (TRT), paired with finasteride (type II 5α-reductase inhibitor), improves body composition, muscle strength, and bone mineral density (BMD) in older men, without inducing prostate enlargement—a side effect associated with TRT. Men with spinal cord injury (SCI) exhibit neuromuscular impairment, muscle atrophy, bone loss, and increased central adiposity, along with low testosterone. However, sparse evidence supports TRT efficacy after SCI.

Methods

This parallel-group, double-blind, placebo-controlled, and randomized clinical trial (RCT) is a pilot study that enrolled men (N = 12) with low to low–normal testosterone and gait impairments after chronic motor-incomplete SCI. Participants received high-dose intramuscular TRT (testosterone-enanthate, 125 mg/week) with finasteride (5 mg/day) vs. vehicle+placebo for 12 months. Change relative to baseline was determined for body composition, musculoskeletal outcomes, and prostate size, with effect sizes calculated between groups using Hedges’ g. Adverse events and feasibility were assessed.

Results

TRT + finasteride consistently increased testosterone (g = 1.16–3.08) and estradiol (g = 0.43–3.48), while concomitantly reducing dihydrotestosterone (g = 0.31–2.27). Very large effect sizes at both 6 and 12 months suggest TRT + finasteride increased whole-body fat-free (lean) mass (+3–4% vs. baseline, g = 2.12–2.14) and knee extensor (KE) whole-muscle cross-sectional area (+8–11% vs. baseline, g = 2.06–2.53) more than vehicle+placebo. Moderate-to-large effect sizes suggest TRT + finasteride increased KE maximal voluntary isometric torque (+15–40% vs. baseline, g = 0.47–1.01) and femoral neck and distal femur BMD from 6 months onward (g = 0.51–1.13), compared with vehicle+placebo, and reduced fat mass 9–14% within the whole-body, trunk, and android (visceral) regions at 12 months (g = 0.77–1.27). TRT + finasteride also produced small effect sizes favoring lesser prostate growth than vehicle+placebo (g = 0.31–0.43). The participant retention, drug compliance, and incidence and severity of adverse events were similar among the groups.

Conclusion

These data provide proof-of-concept and rationale for larger RCTs aimed at discerning the impact of TRT + finasteride on body composition, musculoskeletal health, and physical function in men with SCI, along with effect sizes and variance of responses to assist in planning subsequent trials.

Clinical trial registration

ClinicalTrials.gov, identifier NCT02248701.
Altered neural recruitment during single and dual tasks in athletes with repeat concussion
Authors: Hagen Andrew C. , Tracy Brian L. , Stephens Jaclyn A.
Published: December 2024

Sports-related concussions (SRCs) pose significant challenges to college-aged athletes, eliciting both immediate symptoms and subacute cognitive and motor function impairment. While most symptoms and impairments resolve within weeks, athletes with repeat SRCs may experience heightened risk for prolonged recovery trajectories, future musculoskeletal injuries, and long-term neurocognitive deficits. This study aimed to investigate the impact of repeat SRCs on dual task performance and associated neural recruitment using functional near-infrared spectroscopy (fNIRS). A total of 37 college-aged athletes (ages 18–24) participated in this cross-sectional observational study, 20 with a history of two or more SRCs, and 17 controls that had never sustained an SRC. Participants completed the Neuroimaging-Compatible Dual Task Screen (NC-DTS) while neural recruitment in the frontoparietal attention network and the primary motor and sensory cortices was measured using fNIRS. Athletes with repeat SRCs exhibited comparable single task and dual task performance to control athletes. Neuroimaging results indicated altered neural recruitment patterns in athletes with repeat SRCs during both single and dual tasks. Specifically, athletes with repeat SRCs demonstrated increased prefrontal cortex (PFC) activation during single motor tasks compared to controls (p < 0.001, d = 0.47). Conversely, during dual tasks, these same athletes exhibited reduced PFC activation (p < 0.001, d = 0.29) compared to their single task activation. These findings emphasize that while athletes with repeat SRCs demonstrate typical single and dual task performance, persistent alterations in neural recruitment patterns suggest ongoing neurophysiological changes, possibly indicating compensatory neural strategies and inefficient neural resource allocation, even beyond symptom resolution and medical clearance.