bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance
Authors: Forró Barbara , Kajtár Béla , Lacza Ágnes , Kereskai László , Vida Livia , Kőszegi Balázs , Urbán Péter , Kun József , Gyenesei Attila , Kosztolányi Szabolcs , Kehl Dániel , Jáksó Pál
Published: February 2025

Introduction

CD20+ T-cells were described firstly in peripheral blood and later in bone marrow in patients with hematological tumors, and certain immune-mediated diseases. During our hematological diagnostic work, this peculiar subgroup of lymphocytes has been consistently observed associated with untreated monoclonal gammopathy of undetermined significance (MGUS) and myeloma (MM). Despite the expanding literature data, the exact function of CD20+ T cells remains unclear.

Methods

We investigated the incidence of CD20+ T-cells in MGUS (n=27), and MM using a larger cohort (n=125) and compared it with control bone marrow samples (n=39). We examined their presence before and after treatment in 32 cases with flow cytometry. Comprehensive flow cytometric analysis included the examination of functional (T-cell activation, cytotoxic molecules and T-cell exhaustion) and maturation markers in a large number of cases. In addition RNA sequencing and subsequent bioinformatics analyses were carried out to detect differentially expressed (DE) genes of FACS sorted CD20+ T-cells versus CD20- T-cells.

Results and discussion

We found that CD20+ T-cells are phenotypically and transcriptionally different from CD20- T-cells. Elevated incidence of CD20+ T-cells in MGUS and MM and the expression of CD8, NKG2D, and CD28 suggests anti-tumor functionality. Increased PD-1 expression indicates T-cell exhaustion which was mostly detected in the samples of patients with a higher tumor percentage. The majority of CD20+ T-cells are effector or effector memory T-cells. Some of the differentially expressed genes suggest antitumor function via regulating T-cell activation pathways, while other genes involved in tumor escape from immune surveillance by suppressing T-cells or by reprogramming T-cells toward T-cell exhaustion. Our findings suggest that CD20+ T-cells may play a vital role both in immune surveillance and immune escape contributing to progression of multiple myeloma.
PKR modulates sterile systemic inflammation-triggered neuroinflammation and brain glucose metabolism disturbances
Authors: Cheng Wai-Yin , Lee Xin-Zin , Lai Michael Siu-Lun , Ho Yuen-Shan , Chang Raymond Chuen-Chung
Published: February 2025

Sterile systemic inflammation may contribute to neuroinflammation and accelerate the progression of neurodegenerative diseases. The double-stranded RNA-dependent protein kinase (PKR) is a key signaling molecule that regulates immune responses by regulating macrophage activation, various inflammatory pathways, and inflammasome formation. This study aims to study the role of PKR in regulating sterile systemic inflammation-triggered neuroinflammation and cognitive dysfunctions. Here, the laparotomy mouse model was used to study neuroimmune responses triggered by sterile systemic inflammation. Our study revealed that genetic deletion of PKR in mice potently attenuated the laparotomy-induced peripheral and neural inflammation and cognitive deficits. Furthermore, intracerebroventricular injection of rAAV-DIO-PKR-K296R to inhibit PKR in cholinergic neurons of ChAT-IRES-Cre-eGFP mice rescued the laparotomy-induced changes in key metabolites of brain glucose metabolism, particularly the changes in phosphoenolpyruvate and succinate levels, and cognitive impairment in short-term and spatial working memory. Our results demonstrated the critical role of PKR in regulating neuroinflammation, brain glucose metabolism and cognitive dysfunctions in a peripheral inflammation model. PKR could be a novel pharmacological target for treating systemic inflammation-induced neuroinflammation and cognitive dysfunctions.
Identification and validation of neutrophil-related biomarkers in acute-on-chronic liver failure
Authors: Lin Wei , Chen Yongping , Lu Mingqin , Peng Cheng , Chen Xiang , Liu Xiaoqin , Wang Yunyun
Published: February 2025

Dysfunction of peripheral blood neutrophils occurs in acute-on-chronic liver failure (ACLF). However, the molecular mechanisms of neutrophils involved in the pathophysiology of the ACLF remains poorly understood. Data downloaded from the GEO database (GSE142255) was used to identify both ACLF and neutrophil-related genes with the help of the limma package and Weighted Gene Co-Expression Network Analysis (WGCNA) algorithms. The analysis identified 288 ACLF-related differentially expressed genes (DEGs) in the circulating blood cells. Among these, three genes were found to be related to neutrophils and were identified as diagnostic genes, exhibiting high diagnostic efficacy as evidenced by an area under the curve (AUC) value of 1. Among these, matrix metallopeptidase-9 (MMP9) and S100 calcium binding protein A12 (S100A12) were upregulated, whereas C-C chemokine ligand 5 (CCL5) was downregulated in circulating immune cells from patients with ACLF compared to those from healthy controls. These findings were corroborated using an additional GEO dataset, GSE156382. The expression levels of the three key genes demonstrated a correlation with both ferroptosis and cuprotosis. Among the three diagnostic genes, only MMP9 was validated as differentially expressed through both quantitative real-time PCR (qRT-PCR) and western blot. Moreover, a significant elevation in plasma MMP9 levels was observed in patients with ACLF compared to those with chronic hepatitis B (CHB) and acute decompensated cirrhosis (AD). Notably, ACLF patients exhibiting elevated MMP9 levels (>175.8 ng/mL) experienced higher short-term mortality rates within both 30 and 90 days (p<0.001). In addition, a total of 21 drugs targeting the three diagnostic genes were identified from the Drug Bank database. Finally, the Kinase-TF-mRNA-miRNA network was constructed utilizing Cytoscape software. This study represents the initial application of WGCNA algorithms to identify novel biomarkers related to neutrophils in ACLF. Our findings offer new perspectives on the role of neutrophil in the pathogenesis of ACLF. However, additional research is required to substantiate the effects of these key genes and therapeutic agents on ACLF.
Expression of SIRPα-Fc by oncolytic virus enhances antitumor efficacy through tumor microenvironment reprogramming
Authors: Yang Qingzhe , Shu Yongheng , Chen Yanwei , Qi Zhongbing , Hu Shichuan , Zhang Yao , Qin Yu , Xu Xianglin , Hu Jianchuan , Huang Anliang , Cheng Ping
Published: February 2025

Oncolytic viruses (OVs) selectively replicate within tumors, directly killing cancer cells and promoting a systemic immune response by releasing tumor antigens. These features make OVs a promising approach in tumor immunotherapy, offering targeted treatment with fewer side effects. Despite these advantages, OVs are primarily administered via intratumoral injection, limiting their effectiveness for advanced, systemic cancers. Among OVs, oncolytic adenoviruses (oAdVs) are the most widely studied due to their well-understood gene regulation, safety, and stability. In this study, a modified oAdV vector, pDC316-oAd-SA, was engineered to express the SIRPα-mIgG1Fc gene, designed to remodel tumor-associated macrophages (TAMs) and enhance anti-tumor immunity. This vector, along with a control virus (Ad-ON), was evaluated both in vitro and in vivo. The modified oAd-SA significantly improved macrophage phagocytosis and showed superior tumor regression in murine models. Additionally, while both oAdVs increased T cell infiltration in the tumor microenvironment, oAd-SA specifically enhanced T cell immune function. The study also revealed that oAdVs modulate TAMs differently across tumor types, with oAd-SA therapy particularly increasing TAM phagocytosis and promoting an anti-tumor response.
Cross-protectivity of henipavirus soluble glycoprotein in an in vivo model of Nipah virus disease
Authors: Findlay-Wilson Stephen , Thakur Nazia , Crossley Lucy , Easterbrook Linda , Salguero Francisco J. , Ruedas-Torres Ines , Fotheringham Susan , Kennedy Emma , Bailey Dalan , Dowall Stuart
Published: February 2025

Introduction

Nipah virus (NiV) is one of a group of highly pathogenic viruses classified within the Henipavirus genus. Since 2012 at least 11 new henipa-like viruses have been identified, including from new locations and reservoir hosts; the pathogenicity of these new viruses has yet to be determined, but two of them have been associated with morbidity, including fatalities.

Methods

The efficacy and cross-reactivity of two vaccine candidates derived from the soluble glycoproteins of both NiV and Hendra virus (HeV) was evaluated in our recently established hamster model.

Results

Both vaccine preparations resulted in strong humoral responses against NiV antigenic targets, demonstrating cross-reactive immunity. Efficacy was determined through challenge of hamsters with NiV Malaysian (NiV-M) strain. 100% of the hamsters survived a lethal challenge dose after prime/boost immunisation with glycoproteins derived from both NiV and HeV in the presence of adjuvant, with clinical signs and pathology being significantly reduced in immunised animals.

Discussion

This is first time the NiV and HeV soluble glycoproteins have been compared in the NiV-M hamster challenge model in the presence of Alhydrogel and AddaVax, providing evidence that glycoproteins from closely related henipavirus species can provide cross-protectivity against infection from alternate henipaviruses, supporting the potential of an effective pan-henipavirus vaccine for use in a frontline outbreak response.
HLA allele and haplotype frequencies of eight Indian populations based on 130,518 registered stem cell donors
Authors: Solloch Ute V. , Kaniyath Madhusoodhanan Chinma , Lange Vinzenz , Sauter Jürgen , Jagannathan Latha , Paul Patrick , Fernández-Viña Marcelo A. , Schmidt Alexander H.
Published: February 2025

Introduction

In hematopoietic stem cell transplantation, optimal results are achieved when donors and patients are matched regarding their human leukocyte antigen (HLA) genes. Population-specific HLA allele and haplotype frequency distributions determine the probabilities to find matched donors in a stem cell donor registry of given size and ethnic composition.

Methods

To evaluate the needs of Indian patients with regard to future donor recruitment, we analyzed a large data set of n=130,518 potential stem cell donors registered with DKMS-BMST, a Bangalore-based donor registry with nationwide donor recruitment activities. We defined 8 subpopulations by native language and state of origin of both parents. The subpopulations comprised four samples belonging to the Dravidian language family (native language: Kannada/state of origin: Karnataka, Tamil/Tamil Nadu, Telugu/Andhra Pradesh and Malayalam/Kerala), and four samples belonging to the Indo-Aryan language group (Bengali/West Bengal, Gujarati/Gujarat, Hindi/Uttar Pradesh, Marathi/Maharashtra). The precise definition of subpopulations and large sample sizes between n=5,808 (Telugu/Andhra Pradesh) and n=14,866 (Malayalam/Kerala) are strengths of our study. Our results regarding HLA allele and haplotype frequencies refine published data.

Results and Discussion

In terms of genetic relatedness, we observed a division of the subpopulations into a Southern and a Northwestern Indian cluster and the Bengali/West Bengal sample which differed significantly from the seven other subpopulations. Patients from Southern Indian populations are the main beneficiaries from the DKMS-BMST registry in the current ethnic composition. A more even nationwide coverage will be achieved in the future with the opening of local recruitment offices in different parts of India.
Advances in primary large B-cell lymphoma of immune-privileged sites
Authors: Wang Liao , Guo Meiru , Hou Shuling
Published: February 2025

Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) encompasses a spectrum of relatively rare aggressive B-cell lymphomas, such as primary central nervous system lymphoma (PCNSL), primary testicular large B-cell lymphoma (PTL), and primary vitreoretinal large B-cell lymphoma (PVRL). Macroscopically, the development of IPI-LBCL may be associated with the dysfunction of meningeal lymphatic vessels (mLVs) and the perivascular channel system formed by astrocytes. Microscopically, mutation in MYD88 and CD79B genes plays a pivotal role in the pathogenesis of IP-LBCL. Pathological examination remains the cornerstone for establishing a diagnosis of IP-LBCL. Moreover, traditional imaging is now supplemented by a suite of advanced diagnostic methods, including cytological, genetic, immunological, multiple omics, and molecular biological, which collectively enhance the diagnostic accuracy of IP-LBCL. Despite these advancements, the high recurrence rates and attendant high mortality rates pose significant challenges to achieving long-term survival in IP-LBCL patients. However, the emergence of novel therapeutic agents, such as Bruton’s tyrosine kinase inhibitors (BTKi), immune checkpoint inhibitors, immunomodulators, and anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has offered promising new avenues for the treatment of IP-LBCL, demonstrating remarkable anti-tumor efficacy in recent years. This review delves into the epidemiology, pathogenesis mechanisms, diagnosis approaches, therapeutic strategies, and prognosis factors associated with IP-LBCL. It meticulously examines the parallels and divergences between the National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) guidelines, enhancing the professional comprehension of the complexities inherent to IP-LBCL.
Development of a tertiary lymphoid structure-based prognostic model for breast cancer: integrating single-cell sequencing and machine learning to enhance patient outcomes
Authors: Zhang Xiaonan , Li Li , Shi Xiaoyu , Zhao Yunxia , Cai Zhaogen , Ni Ni , Yang Di , Meng Zixin , Gao Xu , Huang Li , Wang Tao
Published: February 2025

Background

Breast cancer, a highly prevalent global cancer, poses significant challenges, especially in advanced stages. Prognostic models are crucial to enhance patient outcomes. Tertiary lymphoid structures (TLS) within the tumor microenvironment have been associated with better prognostic outcomes.

Methods

We analyzed data from 13 independent breast cancer cohorts, totaling over 9,551 patients. Using single-cell RNA sequencing and machine learning algorithms, we identified critical TLS-associated genes and developed a TLS-based predictive model. This model stratified patients into high and low-risk groups. Genomic alterations, immune infiltration, and cellular interactions within the tumor microenvironment were assessed.

Results

The TLS-based model demonstrated superior accuracy compared to traditional models, predicting overall survival. High TLS patients had higher tumor mutation burden and more chromosomal alterations, correlating with poorer prognosis. High-risk patients exhibited a significant depletion of CD4+ T cells, CD8+ T cells, and B cells, as evidenced by single-cell and bulk transcriptomic analyses. In contrast, immune checkpoint inhibitors demonstrated greater efficacy in low-risk patients, whereas chemotherapy proved more effective for high-risk individuals.

Conclusions

The TLS-based prognostic model is a robust tool for predicting breast cancer outcomes, highlighting the tumor microenvironment’s role in cancer progression. It enhances our understanding of breast cancer biology and supports personalized therapeutic strategies.
The role of tumor-associated macrophages in lung cancer
Authors: Zhu Ronghao , Huang Jing , Qian Fenhong
Published: February 2025

Lung cancer remains a leading cause of cancer-related deaths worldwide, necessitating innovative treatments. Tumor-associated macrophages (TAMs) are primary immunosuppressive effectors that foster tumor proliferation, angiogenesis, metastasis, and resistance to therapy. They are broadly categorized into proinflammatory M1 and tumor-promoting M2 phenotypes, with elevated M2 infiltration correlating with poor prognosis. Strategies aimed at inhibiting TAM recruitment, depleting TAMs, or reprogramming M2 to M1 are therefore highly promising. Key signaling pathways, such as CSF-1/CSF-1R, IL-4/IL-13–STAT6, TLRs, and CD47-SIRPα, regulate TAM polarization. Additionally, macrophage-based drug delivery systems permit targeted agent transport to hypoxic regions, enhancing therapy. Preclinical studies combining TAM-targeted therapies with chemotherapy or immune checkpoint inhibitors have yielded improved responses and prolonged survival. Several clinical trials have also reported benefits in previously unresponsive patients. Future work should clarify the roles of macrophage-derived exosomes, cytokines, and additional mediators in shaping the immunosuppressive tumor microenvironment. These insights will inform the design of next-generation drug carriers and optimize combination immunotherapies within precision medicine frameworks. Elucidating TAM phenotypes and their regulatory molecules remains central to developing novel strategies that curb tumor progression and ultimately improve outcomes in lung cancer. Importantly, macrophage-based immunomodulation may offer expanded treatment avenues.
Virological response and predictive factors for antiviral treatment in chronic HBV-related liver disease with low ALT and high HBV DNA
Authors: Ma Lei , Li Yan , Weng Lihan , Xing Huichun
Published: February 2025

Objective

To investigate virological response and predictive factors for antiviral treatment in chronic HBV patients with low ALT and high HBV DNA.

Methods

A retrospective study grouped chronic HBV patients by baseline ALT: ALT > 80 U/L (significantly elevated group, SAG), 40-80 U/L (mildly elevated group, MAG), and ≤ 40 U/L (normal group, NG). Inverse probability treatment weighting balanced confounding factors. Complete virological response (CVR, HBV DNA < 20 IU/mL) and partial virological response (PVR, HBV DNA ≥ 20 IU/mL) were defined. NG subgroup analyses were performed using baseline ALT (cutoff: 30 U/L for males, 19 U/L for females), HBV DNA (cutoff: 7.21 Log10 IU/mL), and Aspartate Aminotransferase to Platelet Ratio Index (cutoff: 0.32). Cox regression identified factors predicting CVR at week 48.

Results

After IPTW, the number of patients in the NG, MAG, and SAG groups was 92, 141, and 284, and the CVR rates at week 48 were 38.05%, 55.26%, and 7analyses 3.32% respectively (p < 0.0001). Weighted Kaplan-Meier analysis showed that the NG group had the lowest probability of achieving CVR at week 48 (p < 0.0001). Particularly, in the NG group, the high-normal ALT subgroup had a higher CVR rate (56.34% (40/71)) than the low-normal ALT subgroup (29.73% (11/37), p = 0.0103), similar to that of the MAG group (p = 0.9871). The low-HBV DNA (82.46% (47/57)) and high-APRI subgroup (63.79% (37/58)) had higher CVR rates than the high-HBV DNA (7.84% (4/51)) and low-APRI subgroup (28% (14/50)) respectively. High HBV DNA and low ALT patients in NG had a CVR of 0% (0/18). Cox regression identified baseline ALT ≤ 30 U/L (males) or ALT ≤ 19 U/L (females), HBV DNA > 7.21 Log10 IU/mL, HBeAg positive state, APRI < 0.32, and a decrease in HBV DNA < 3.49 Log10 IU/mL at 12 weeks as independent adverse predictors of CVR.

Conclusion

The NG group has lower CVR, but the high-normal ALT subgroup performs similarly to MAG. High HBV DNA and low ALT significantly reduce CVR. Key adverse predictors include low ALT, high HBV DNA, HBeAg positivity, low APRI, and suboptimal viral reduction at 12 weeks.
Emission-reduction investment strategies in competitive shipping supply chains under carbon cap-and-trade mechanisms
Authors: Zhang Guangsheng , Zhang Zhaomin , Yuan Hao , Chen Weijie
Published: February 2025

Market-based carbon cap-and-trade mechanisms play a pivotal role in reducing the carbon emissions of shipping logistics companies. Focusing on the issue of emission reduction investment in the competitive shipping logistics service supply chain (SLSSCs) under carbon cap-and-trade, this paper constructs a game theory model for emission reduction investment decision-making in the SLSSC, which comprises two participants-a shipping logistics service provider (SLSP) and a shipping logistics service integrator (SLSI)-discusses the equilibrium strategy of emission reduction investment based on optimization theory, and further explores the benefits of participating entities, consumer surplus, and social welfare under different emission reduction strategies. The findings indicate that: (1) a no-reduction investment strategy, a single-chain investment strategy, and a dual-chain investment strategy can each serve as equilibrium strategies, which are influenced by the interplay among the unit carbon emission trading price, the spillover effect of emission reduction investments, and the associated cost coefficient. (2) Both single-chain and dual-chain emission reduction strategies in the SLSSCs contribute to consumer surplus; however, their impact on social welfare is contingent on the SLSI’s cost coefficient for emission reductionn investments. (3) Under the single-chain equilibrium strategy, the spillover effect from the SLSI’s emission reduction investment has a favorable impact on returns for participants in the non-investing chain, consumer surplus, and social welfare, but adversely affectts returns for participants in the investing chain. Under the dual-chain equilibrium strategy, the spillover effect benefits both chains’ participants’ returns, consumer surplus, and social welfare. In addition, the SLSP’s altruistic inclination enhances participants’ returns, consumer surplus, and social welfare across all strategies.
Choroidal metastases from thoracic cancer: a retrospective study on clinical characteristics and treatment efficacy
Authors: Lin Xiacheng , Zhong Yusheng , Li Haiping , Yang Yating , Liu Ahui , Shi Yajing , Liang Jianhong , Cheng Yong
Published: February 2025

Objective

This study aimed to examine the clinical characteristics of choroidal metastases (CMs) and assess the efficacy of various treatment strategies for CMs in a specific patient cohort.

Methods

This retrospective case series study included 32 patients (38 eyes) diagnosed with CM at the Department of Ophthalmology, Peking University People’s Hospital, between 2009 and 2022. The cohort included 10 male patients (10 eyes) and 22 female patients (28 eyes), with a mean age of 52.53 ± 10.81 years. Detailed medical histories and multiple ophthalmic examinations were performed for all patients, with diagnoses confirmed by two senior ophthalmologists. Clinical characteristics, treatment responses, and follow-up outcomes were analyzed.

Results

Lung cancer was the most common primary tumor (53.1%), with six patients initially presenting with ocular symptoms. Initial ultrasound imaging revealed a mean tumor height of 3.02 mm and a mean basal diameter of 11.09 mm. Optical coherence tomography (OCT) revealed irregular, highly reflective foci with undulating anterior surfaces, and fluorescein angiography (FFA) revealed early choroidal tumor masking and late-phase mottled hyperfluorescence with occasional leakage. Indocyanine green angiography (ICGA) revealed hypofluorescence in early and late phases, with slightly mottled hyperfluorescence in the late phase. The follow-up period ranged from 3 months to 4 years (median 4 months), during which systemic and local treatments effectively controlled or delayed tumor progression in most patients.

Conclusion

Lung and breast cancers are the leading sources of CMs, with bilateral or multifocal lesions more frequently linked to breast cancer. Treatment for CMs should be meticulously individualized and should take into account the patient’s overall condition, tumor burden, and precise tumor location. Local treatment is essential for patients with significant ocular symptoms. A combination of local and systemic treatments has been shown to lead to a more significant reduction in tumor burden.
Exploring the therapeutic potential of “Zhi-Zhen” formula for oxaliplatin resistance in colorectal cancer: an integrated study combining UPLC-QTOF-MS/MS, bioinformatics, network pharmacology, and experimental validation
Authors: Li Yongjing , Chen Ke , Li Qin , Liu Qiaoli , Han Huijie , Liu Hui , Wang Songpo
Published: February 2025

Background

Chemoresistance is a critical factor compromising the survival of patients with colorectal cancer (CRC). The “Zhi-Zhen” formula (ZZF), a traditional prescription developed by Chinese national medicine masters, has been extensively used in clinical practice to treat gastrointestinal cancer. Notably, ZZF has the potential to enhance tumor sensitivity to chemotherapy. Although previous in vitro studies have demonstrated the efficacy of ZZF in overcoming chemoresistance in colorectal cancer (CRC), its precise molecular mechanisms remain poorly understood.

Materials and methods

We used an integrated approach of bioinformatics and network pharmacology to predict the potential active ingredients and targets of ZZF in alleviating chemoresistance. The top five active ingredients identified by degree in the network analysis were validated using mass spectrometry. We then established an oxaliplatin-resistant CRC cell model to explore the potential targets and regulatory mechanisms through which ZZF overcomes chemoresistance at the cellular level.

Results

Network pharmacology and bioinformatics analyses jointly identified 29 active compounds and 13 potential key targets of ZZF, associated with chemoresistance. Among these targets, the differential expression of CASP7 significantly affected the progression-free survival of patients with CRC. We established two oxaliplatin-resistant CRC cell lines and observed an upregulation of CASP7 expression in these resistant cells. Furthermore, ZZF increases the expression and activation of CASP7 in resistant cells, promoting apoptosis, and thereby ameliorating chemoresistance. Additionally, β-catenin knockdown led to an upregulation of CASP7 expression, whereas activation of the Wnt/β-catenin signaling pathway reduced CASP7 protein levels. ZZF decreases the activity of the Wnt/β-catenin signaling pathway by decreasing β-catenin transcription and nuclear localization.

Conclusion

ZZF has potential clinical value in the treatment of chemoresistance in CRC by inhibiting the transcription and nuclear localization of β-catenin, thereby increasing the expression of CASP7 and enhancing the apoptotic response in chemoresistant CRC cells.
Effects of cipepofol on breathing patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients
Authors: Su Rui , Zhang Linlin , Wang Yu-Mei , Miao Ming-Yue , Wang Shuya , Cao Yong , Zhou Jian-Xin
Published: February 2025

Background

Cipepofol is a highly selective gamma-aminobutyric acid A receptor potentiator. As a new sedative drug, detailed studies on its respiratory effects are further needed. The present study aims to investigate the effects of cipepofol on breathing patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients.

Methods

In this one-arm physiological study, cipepofol was initiated at 0.3 mg/kg/h and increased by 0.1 mg/kg/h every 30 min until reaching 0.8 mg/kg/h. Discontinuation criteria were Richmond Agitation and Sedation Scale (RASS) score ≤ −4 or respiratory rate (RR) < 8 breaths/min or pulse oxygen saturation (SpO2) < 90%. The primary outcomes were changes from baseline in respiratory variables [RR, tidal volume (VT), minute ventilation (Vmin), airway occlusion pressure at 100 msec (P0.1), pressure muscle index (PMI), expiratory occlusion pressure (Pocc)] at 30 min after 0.3 mg/kg/h cipepofol infusion. The secondary outcomes included changes in respiratory variables, cardiorespiratory variables, and RASS scores at rates of cipepofol from 0.3 to 0.8 mg/kg/h.

Results

20 patients were enrolled and all of them completed the cipepofol infusion rate at 0.3 mg/kg/h, achieving RASS score of −2 to +1. For the primary outcomes, there was a significant reduction in VT (390.9, [356.6–511.0] vs. 451.6 [393.5–565.9], p = 0.002), while changes in RR (16.7 ± 2.7 vs. 16.2 ± 3.4, p = 0.465) and Vmin (7.2 ± 1.8 vs. 7.5 ± 1.9, p = 0.154) were not significant. The reductions in P0.1 (p = 0.020), PMI (p = 0.019), and Pocc (p = 0.007) were significant. For secondary outcomes, as the infusion rate of cipepofol increased from 0.3 to 0.8 mg/kg/h, there was a further decrease in VT (p = 0.002) and an increase in RR (p < 0.001), while the change in Vmin (p = 0.430) was not significant. RASS score (p < 0.001) was further decreased.

Conclusion

Cipepofol demonstrates the capability to achieve RASS score −2 to +1 in mechanically ventilated adult patients. The effect of cipepofol on breathing patterns was a decrease in VT, while changes in RR and Vmin were insignificant. The effect on respiratory drive and inspiratory effort significantly reduced P0.1, PMI, and Pocc.

Clinical trial registration

ClinicalTrials.gov, identifier NCT06287138. https://clinicaltrials.gov/study/NCT06287138
Healthy lifestyle behaviors and depressive symptoms: a national cross-sectional study of the older adults in China
Authors: Jiao Haojin , Ge-Zhang Shangjie , Yang Jingqi
Published: February 2025

Introduction

This investigation assesses the impact of healthy lifestyle behaviors on depressive symptoms among older adults in China, utilizing data from the 2020 China Health and Retirement Longitudinal Study (CHARLS).

Methods

The analysis included 9,020 valid samples from individuals aged 60 and above. Sleep duration, social participation, and physical exercise were examined as independent variables. Depressive symptoms were measured using the CESD-10 scale, with relationships analyzed through an ordered logistic regression model.

Results

The study reveals significant correlations between healthy lifestyle behaviors — specifically adequate sleep, regular physical exercise, and active social participation — and reduced prevalence of depressive symptoms in the elderly (p < 0.05).

Discussion

These findings underscore the potential of healthy lifestyle interventions as key strategies in alleviating the mental health burden among China’s aging population. Integration of these results into public health policies is recommended to enhance the mental well-being of older adults.
Understanding the microbiome–crop rotation nexus in karst agricultural systems: insights from Southwestern China
Authors: Wang Bin , Shang Nianjie , Feng Xinwei , Hu Zongling , Li Pengfei , Chen Yi , Hu Binbin , Ding Mengjiao , Xu Junju
Published: February 2025

Understanding how soil properties and microbial communities respond to crop rotation is essential for the sustainability of agroecosystems. However, there has been limited research on how crop rotation alters below-ground microbial communities in soils with serious bacterial wilt within the karst agricultural system. This study investigated the effects of continuous planting of corn, tobacco, and tobacco–corn rotation on soil microbial communities in the karst regions of Southwestern China. High-throughput sequencing was used to evaluate the responses of the soil microbial community structure to crop monoculture and rotation patterns. As expected, the tobacco–corn rotation mitigated the negative effects of continuous cropping and reduced soil acidification. The tobacco–corn rotation also significantly altered the composition of microbial communities and promoted plant growth by fostering a higher abundance of beneficial microorganisms. The predominant bacteria genera Sphingomonas and Gaiella and the predominant fungal genera Mortierella and Saitozyma were identified as discriminant biomarkers that are critical to soil ecosystem health. pH, available potassium (AK), and available phosphorus (AP) were the primary soil factors related to the soil microbiome assembly. This study aimed to demonstrate the association between crop rotation and microbiomes, suggesting that altering cultivation patterns could enhance karst agricultural systems.
Identification of in planta bioprotectants against Fusarium wilt in Medicago sativa L. (lucerne) from a collection of bacterial isolates derived from Medicago seeds
Authors: Herath Dissanayakalage Shenali Subodha , Kaur Jatinder , Achari Saidi R. , Sawbridge Timothy I.
Published: February 2025

Fusarium wilt caused by Fusarium oxysporum f. sp. medicaginis (Fom) is an important disease affecting lucerne/alfalfa cultivations worldwide. Medicago sativa L. (lucerne) is one of the major legume crops in global forage industry. This study aimed to identify bacteria capable of biologically controlling the wilt pathogen through a comprehensive screening of bacterial isolates obtained from domesticated and wild growing Medicago seeds. Using a multi-tiered evaluation pipeline, including in vitro, soil-free and potting mix-based pathogenicity and bioprotection assay systems, the bioprotection efficacy of 34 bacterial isolates derived from Medicago seeds was initially evaluated against six Fusarium strains in vitro. Fusarium oxysporum (Fo) F5189, which has previously been characterized as a Fusarium oxysporum f. sp. medicaginis isolate causing Fusarium wilt in lucerne was selected for in planta assays. Lucerne cultivars Grazer and Sequel, representing susceptible and resistant genotypes were chosen to assess the disease progression. Pathogenicity and bioprotection time-course studies were conducted to understand the temporal dynamics of host-pathogen interactions and efficacy of the bioprotectants. The disease symptoms were scored using a disease rating index developed in this study. The results indicated variability in bioprotection efficacy across bacterial isolates, with some strains suppressing disease in both soil-free and potting mix-based systems. Paenibacillus sp. (Lu_MgY_007; NCBI: PQ756884) and Pseudomonas sp. (Lu_LA164_018; NCBI: PQ756887) were identified as promising bioprotectants against Fusarium wilt under tested growth conditions. The time-course studies highlighted the critical role of persistent biocontrol activity and precise timing of biocontrol application for achieving long-term disease suppression. Overall, the observed reduction in disease severity underscores the potential of these bioprotectants as sustainable strategies for managing Fusarium wilt in lucerne cultivars. However, comprehensive molecular-level analyses are warranted to elucidate the underlying pathogenicity and bioprotection mechanisms, offering valuable insights for the development of more precise and effective future biocontrol strategies in agricultural systems.
Development of an enzyme-linked immunosorbent assay (ELISA) for determining neutrophil elastase (NE) – a potential useful marker of multi-organ damage observed in COVID-19 and post-Covid-19 (PCS)
Authors: Adamiec-Mroczek Joanna , Kluz Joanna , Chwałek Sandra , Rabczyński Maciej , Gostomska-Pampuch Kinga , Lewandowski Łukasz , Misiuk-Hojło Marta , Ponikowska Beata , Chourasia Goutam , Dumas Ilias , Gamian Andrzej , Fiodorenko-Dumas Żanna , Konopska Bogusława , Gola Agnieszka , Konikowska Klaudia , Strub Daniel , Bronowicka-Szydełko Agnieszka , Madziarska Katarzyna
Published: February 2025

Background

The ongoing post-COVID-19 syndrome (PCS) epidemic, causing complications of diverse etiology, necessitates the search for new diagnostic markers and the development of widely accessible methods for their detection. This would enable the prognosis of PCS progression and faster implementation of targeted treatments. One potential marker is neutrophil elastase (NE), whose elevated levels in the blood during PCS may result from organ damage caused by increased secretion of severe inflammatory mediators or amyloidosis resulting from the interaction of NE with SARS-CoV-2. The aim of this publication is to present a step-by-step method for designing an enzymatic ELISA test, enabling the quantitative assessment of NE in the blood serum of patients.

Methods

NE was measured using the designed ELISA test.

Results

The study outlines all the steps necessary for designing and optimizing the ELISA test, including the selection of standards, primary and secondary antibodies, and their dilutions. Using the test, elevated NE levels were demonstrated in patients with advanced-stage diabetic nephropathy after symptomatic COVID-19, compared to a relative group of patients sampled before COVID-19.

Conclusion

The undertaken efforts enabled the development of a test with high performance parameters (initially set sensitivity: ≥40 pg/μL; intra-assay precision: 7%; inter-assay precision <20%). No significant cross-reactivity with other tested proteins was observed. Serial dilution of plasma samples resulted in a proportional decrease in signal intensity.
Protective and risk factors in daily life associated with cognitive decline of older adults
Authors: Tong Fang , Yang Hao , Yu Haidong , Sui Le-wen , Yao Jing-yuan , Shi Chen-lei , Yao Qiao-yuan , Shi Mei-fang , Qian Cheng-lang , Li Gang , Zhao Chao , Wang Hui-jing
Published: February 2025

Background

Cognitive decline is a chronic condition which is characterized by a loss of the ability to remember, learn, and pay attention to complex tasks. Many older people are now suffering from cognitive decline, which decreases life quality and leads to disability. This study aimed to identify the risk and protective factors for cognitive decline of the older people from daily life and establish a predictive model using logistic regression.

Methods

We investigated 3,790 older people with health examination and questionnaires which included information associated with physical condition, lifestyle factors, and cognitive status. Single-factor comparison, principal component analysis with a Manova-Wilk test, multiple linear regression, and logistic regression were performed to filter the risk and protective factors regarding cognitive decline of older individuals. Then a predictive model using logistic regression was established based on the most significant protective and risk factors.

Results

We found a significant separation along the coordinate axis between people with normal and declined cognition by principal component analysis, as confirmed by the Manover-Wilk test. Single-factor comparison, multiple linear regression and logistic regression implied that gender, age, hypertension level, height, dietary habit, physical-exercise duration, physical-exercise history, and smoking history could be closely linked with cognitive decline. We also observed significant differences in height, physical exercise duration, physical-exercise years, and smoking years between the male and female of the participants. ROCs of the predictive model by logistic regression were plotted, with AUC values of 0.683 and 0.682, respectively, for the training and testing sets. Although an effective predictive model is thought to have AUC over 0.7, we still believe that the present model is acceptable because the value is close to the threshold.

Conclusion

The protective factors of cognitive decline for older people were male gender, height, keeping moderate exercising, and nicotine stimulation, and the risk factors included age, female gender, vegetarianism and hypertension. Except for the genetic factor, differences in lifestyle, such as smoking and exercise habits, may contribute to the observed differences in cognitive function between genders. The significant results could be utilized in the practice for the early intervention of cognitive decline in aged people.
A longitudinal study on the effect of aerobic exercise intervention on the inhibitory control in college students with internet addiction
Authors: Wang Yi , Li Xiangkun
Published: February 2025

Objectives

This study aimed to investigate the effects of aerobic exercise on reactive inhibitory control in college students with internet addiction, examining both behavioral and electrophysiological changes over time.

Methods

A longitudinal study design was adopted, involving 48 male college students with internet addiction who were randomly assigned to either a control group or an experimental group. Participants in the experimental group engaged in 40 min aerobic cycling sessions three times per week for 12 weeks, while the control group maintained their usual physical activity levels without any intervention. A 3 × 2 × 3 mixed-factorial design was utilized, incorporating three time points (pre-experiment, 6 and 12 weeks), two groups (control and experimental), and three electrode sites (Fz, F3, F4). This design enabled the examination of the effects of aerobic exercise on reactive inhibitory control and its temporal dynamics in college students with internet addiction.

Results

A significant main effect of group was observed. Specifically, the experimental group demonstrated a significantly higher Nogo accuracy rate compared to the control group at both the mid-test (P < 0.01) and post-test (P < 0.001). Within the experimental group, the Nogo accuracy rate at the mid-test and post-test was significantly higher than at the pre-test (P < 0.001), with the post-test accuracy rate also significantly higher than the mid-test (P < 0.05). Time-frequency analysis revealed that, under the Nogo task, the energy values in the beta frequency band during the early (100–500 ms) and late (600–750 ms) time windows were significantly higher at the mid-test and post-test compared to the pre-test (P < 0.05), with the post-test values significantly exceeding those at the mid-test (P < 0.05).

Conclusion

(1) Moderate-intensity aerobic exercise significantly improves reactive inhibitory control in college students with internet addiction, with the magnitude of improvement increasing over the duration of the intervention. (2) Increased beta band energy during the early (100–500 ms) and late (600–750 ms) time windows serve as a key neurophysiological indicator of this enhancement.
A spatial and temporal transformer-based EEG emotion recognition in VR environment
Authors: Li Ming , Yu Peng , Shen Yang
Published: February 2025

With the rapid development of deep learning, Electroencephalograph(EEG) emotion recognition has played a significant role in affective brain-computer interfaces. Many advanced emotion recognition models have achieved excellent results. However, current research is mostly conducted in laboratory settings for emotion induction, which lacks sufficient ecological validity and differs significantly from real-world scenarios. Moreover, emotion recognition models are typically trained and tested on datasets collected in laboratory environments, with little validation of their effectiveness in real-world situations. VR, providing a highly immersive and realistic experience, is an ideal tool for emotional research. In this paper, we collect EEG data from participants while they watched VR videos. We propose a purely Transformer-based method, EmoSTT. We use two separate Transformer modules to comprehensively model the temporal and spatial information of EEG signals. We validate the effectiveness of EmoSTT on a passive paradigm collected in a laboratory environment and an active paradigm emotion dataset collected in a VR environment. Compared with state-of-the-art methods, our method achieves robust emotion classification performance and can be well transferred between different emotion elicitation paradigms.
Initial insights into post-contrast enhancement in ultra-low-field MRI: Case Report
Authors: Altaf Ahmed , Alam Muhammad Sami , Khan Sibgha , Azan Ali , Mubarak Fatima , Knopp Edmond , Siddiqui Khan , Enam Syed Ather
Published: February 2025

Brain tumors represent a significant burden, particularly in low- and middle-income countries (LMICs) where access to neuroimaging techniques is often limited. Conventional MRI machines are expensive and bulky, posing a significant challenge in the diagnosis and treatment of brain tumors in LMICs. However, an emerging technology, ultra-low field magnetic resonance imaging (pULF-MRI), has the potential to address this limitation. This study aimed to evaluate the feasibility and effectiveness of post-contrast enhancement in a pULF-MRI scanner for brain tumor imaging in LMICs. A single case study was conducted, and post-contrast enhancement was successfully achieved, revealing the presence of a tumor which was subsequently confirmed on biopsy. To our knowledge, this is the first study to demonstrate the feasibility of post-contrast enhancement in a pULF-MRI scanner for brain tumor imaging. This technology has the potential to significantly improve access to neuroimaging in LMICs, leading to earlier diagnosis and more effective treatment of brain tumors. These promising results suggest that further studies are warranted to explore the potential of pULF-MRI for large-scale screening and diagnosis of brain tumors in LMICs. This can provide a future roadmap for neuroimaging in LMICs, providing a cost-effective and accessible way to diagnose and treat brain tumors, leading to improved healthcare outcomes with a further prospective clinical trial.
The characteristics of brain function alterations in patients with chronic prostatitis/chronic pelvic pain syndrome across varying symptom severities evaluated by NIH-CPSI
Authors: Ge Shengyang , Xiang Yunting , Hua Xuyun , Wang Zening , Hu Qingfeng , Guo Yijun , Huang Jingqiang , Zhao Chengpeng , Wu Jiajia , Wang Xianli , Sun Chuanyu
Published: February 2025

Background

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition in urology characterized by chronic pain. The pathogenesis of CP/CPPS remains unclear.

Methods

We enrolled 45 eligible CP/CPPS patients and 45 healthy volunteers. We evaluated their resting-state fMRI data using a comprehensive set of parameters, such as Regional Homogeneity (ReHo) and Degree Centrality (DC), to detect brain abnormalities and identify potential correlates with the clinical manifestations of CP/CPPS. We further categorized the patients into subgroups according to their scores of NIH-CPSI to elucidate the brain changes associated with differing symptom severities.

Results

Profound alterations in brain function were observed in patients with CP/CPPS. These changes involved multiple brain regions identified by DC analysis, including the right anterior cingulate cortex (ACC), left inferior frontal opercular cortex, left amygdala, right middle frontal cortex, and bilateral insula. ReHo analysis revealed significant changes in the right thalamus, left inferior frontal triangular cortex, right superior temporal pole, left ACC, and right superior frontal cortex (cluster >20 voxels, GRF correction, p < 0.05). Analysis using ReHo and DC revealed that brain alterations associated with varying symptom severities were localized in pain perception and modulation regions. Specifically, the DC values in the right ACC showed a linear correlation with the severity of symptoms measured by the NIH-CPSI (AUC = 0.9654, p < 0.0001).

Conclusion

In CP/CPPS, we first discovered differences in brain function among patients with varying degrees of severity. The brain alterations of DC in the right ACC might be a potential biomarker for diagnosing and assessing disease severity.