bluuebunny/crossref_metadata_2025 huggingface dataset:
Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populations
Authors: Alyamani Manar , Kadivar Mohammad , Erjefält Jonas , Johansson-Lindbom Bengt , Duan Rui-Dong , Nilsson Åke , Marsal Jan
Published: January 2023

Background and aim

Alkaline sphingomyelinase (NPP7) is expressed by intestinal epithelial cells and is crucial for the digestion of dietary sphingomyelin. NPP7 also inactivates proinflammatory mediators including platelet-activating factor and lysophosphatidylcholine. The aim of this study was to examine a potential role for NPP7 in the homeostasis of the intestinal immune system.

Methods

We quantified the numbers of B-lymphocytes, plasma cells, T-lymphocytes including regulatory T-lymphocytes (Tregs), natural killer cells, dendritic cells, macrophages, and neutrophils, in the small and large intestines, the mesenteric lymph nodes and the spleens of heterozygous and homozygous NPP7 knockout (KO) and wildtype (WT) mice. Tissues were examined by immunohistochemistry and stainings quantified using computerized image analysis.

Results

The numbers of both small and large intestinal CD3ε+, CD4+, and CD8α+ T-lymphocytes were significantly higher in NPP7 KO compared to WT mice (with a dose-response relationship in the large intestine), whereas Treg numbers were unchanged, and dendritic cell numbers reduced. In contrast, the numbers of CD3ε+ and CD4+ T-lymphocytes in mesenteric lymph nodes were significantly reduced in NPP7 KO mice, while no differences were observed in spleens. The numbers of B-lymphocytes, plasma cells, natural killer cells, macrophages, and neutrophils were similar between genotypes.

Conclusion

NPP7 contributes to the regulation of dendritic cell and T-lymphocyte numbers in mesenteric lymph nodes and both the small and large intestines, thus playing a role in the homeostasis of gut immunity. Although it is likely that the downstream effects of NPP7 activity involve the sphingomyelin metabolites ceramide and spingosine-1-phosphate, the exact mechanisms behind this regulatory function of NPP7 need to be addressed in future studies.
The potential role of short chain fatty acids improving ex vivo T and CAR-T cell fitness and expansion for cancer immunotherapies
Authors: González-Brito Adrián , Uribe-Herranz Mireia
Published: January 2023

Adoptive cell therapies, like tumor-infiltrating lymphocytes or chimeric antigen receptor T cells, have become an important immunotherapeutic approach against cancer. One of the main struggles of T cell immunotherapies is how to obtain the most effective T cell phenotype, persistence, and differentiation potential to infuse into patients. Adjusting the T cell ex vivo cell culture conditions is a key factor to increase and improve the efficacy of cellular immunotherapies. In this review, we have summarized the ex vivo impact of short chain fatty acids, a group of gut microbiota derived metabolites, on T cell culture and expansion for immunotherapies. There is a complex gut microbiota-immune system interaction that can affect antitumor immunotherapy efficacy. Indeed, gut microbiota derived metabolites can modulate different biological functions in the immune system local and systemically.
Targeting HIV-1 reservoirs in T cell subsets
Authors: Li Min , Budai Marietta M. , Chen Min , Wang Jin
Published: January 2023

The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral re-activation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found that treatments of HIV-1 infection by suppressive antiretroviral therapy (ART) led to the establishment of latent HIV reservoirs in naïve, central memory and effector memory T cells. Moreover, SECH treatments could clear latent HIV-1 reservoirs in these different T cell subsets of humanized mice. Co-culture studies showed that T cell subsets latently infected by HIV-1, but not uninfected bystander cells, were susceptible to cell death induced by SECH treatments. Our study suggests that the SECH strategy is effective for specific targeting of latent HIV-1 reservoirs in different T cell subsets.
Radiation therapy in the era of immune treatment for hepatocellular carcinoma
Authors: Chen Lingjuan , Zhang Ruiguang , Lin Zhenyu , Tan Qiaoyun , Huang Zhiyong , Liang Binyong
Published: January 2023

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in recent years and provide new opportunities to treat hepatocellular carcinoma (HCC). To date, several ICIs have been approved by the FDA for advanced HCC in first-line or second-line therapy. Downstaging conversion therapy for potentially resectable HCC to provide opportunities for surgical intervention is challenging. ICIs have become a hot spot in this field due to their high response rate. However, HCC has various etiologies and can evade the immune system through multiple mechanisms, which limit the efficacy of ICI monotherapy and demand novel combination strategies. Radiation therapy (RT) is also a candidate for conversion therapy in HCC and is currently gaining increasing attention as a good combination partner with ICIs due to its ability to modulate the tumor microenvironment. In this review, we illustrate the current indications for ICIs and RT in HCC, the rationale for their synergistic combination, and the current clinical trials in combination therapy. We also speculate on predictive biomarkers and novel future strategies to further enhance the efficacy of this combination. This review aims to provide references for future research on radiation and immunotherapy to arrive at a promising new era of HCC treatment.
High levels of kappa free light chain synthesis predict cognitive decline in relapsing-remitting multiple sclerosis
Authors: Rosenstein Igal , Axelsson Markus , Novakova Lenka , Rasch Sofia , Blennow Kaj , Zetterberg Henrik , Lycke Jan
Published: January 2023

Background

Evolving evidence suggests that measurement of cerebrospinal fluid (CSF) kappa free light chain (KFLC) synthesis has high diagnostic sensitivity and specificity for multiple sclerosis (MS), but its prognostic ability is less investigated. The usefulness of KFLC in predicting cognitive impairment (CI) is still unknown.

Methods

In a monocentric longitudinal retrospecitve cohort study, KFLC-index ([CSF KFLC/serum KFLC]/[CSF albumin/serum albumin]) measured by latex-enhanced immunonephelometry was prospectively determined as part of the diagnostic workup in patients with early relapsing-remitting MS (RRMS, n=77). The ability of KFLC-index to predict information processing speed (IPS) worsening as assessed with the symbol digit modalities test (SDMT) was investigated in univariable and multivariable models.

Results

In patients with KFLC-index>100 (n=31), 11 subjects (35.5%) showed reduced SDMT scores by ≥8 points at follow-up (mean follow-up time 7.3 ± 2.6 years), compared with their baseline scores (p=0.01). Baseline KFLC-index>100 was strongly associated with a higher hazard of SDMT score reduction at follow-up (adjusted hazard ratio 10.5, 95% confidence interval 2.2-50.8, p=0.003; median time to SDMT reduction 7 years).

Conclusion

Intrathecal KFLC synthesis has become an attractive diagnostic tool for MS. We show for the first time that in a real-world setting of early RRMS, KFLC-index predicted cognitive decline. Whether this predictive ability of KFLC-index also concerns other cognitive domains than IPS, warrants further investigations.
Significance of logistic regression scoring model based on natural killer cell-mediated cytotoxic pathway in the diagnosis of colon cancer
Authors: Ye Zhen , Zhang Huanhuan , Liang Jianwei , Yi Shuying , Zhan Xianquan
Published: January 2023

Background

The poor clinical accuracy to predict the survival of colon cancer patients is associated with a high incidence rate and a poor 3-year survival rate. This study aimed to identify the poor prognostic biomarkers of colon cancer from natural killer cell-mediated cytotoxic pathway (NKCP), and establish a logistical regression scoring model to predict its prognosis.

Methods

Based on the expressions and methylations of NKCP-related genes (NRGs) and the clinical information, dimensionality reduction screening was performed to establish a logistic regression scoring model to predict survival and prognosis. Risk score, clinical stage, and ULBP2 were used to establish a logistic regression scoring model to classify the 3-year survival period and compare with each other. Comparison of survival, tumor mutation burden (TMB), estimation of immune invasion, and prediction of chemotherapeutic drug IC50 were performed between low- and high-risk score groups.

Results

This study found that ULBP2 was significantly overexpressed in colon cancer tissues and colon cancer cell lines. The logistic regression scoring model was established to include six statistically significant features: S = 1.70 × stage – 9.32 × cg06543087 + 6.19 × cg25848557 + 1.29 × IFNA1 + 0.048 × age + 4.37 × cg21370856 − 8.93, which was used to calculate risk score of each sample. The risk scores, clinical stage, and ULBP2 were classified into three-year survival, the 3-year prediction accuracy based on 10-fold cross-validation was 80.17%, 67.24, and 59.48%, respectively. The survival time of low-risk score group was better than that of the high-risk score group. Moreover, compared to high-risk score group, low-risk score group had lower TMB [2.20/MB (log10) vs. 2.34/MB (log10)], higher infiltration score of M0 macrophages (0.17 vs. 0.14), and lower mean IC50 value of oxaliplatin (3.65 vs 3.78) (p < 0.05).

Conclusions

The significantly upregulated ULBP2 was a poor prognostic biomarker of colon cancer. The risk score based on the six-feature logistic regression model can effectively predict the 3-year survival time. High-risk score group demonstrated a poorer prognosis, higher TMB, lower M0 macrophage infiltration score, and higher IC50 value of oxaliplatin. The six-feature logistic scoring model has certain clinical significance in colon cancer.
Gut microbiota and its metabolites – molecular mechanisms and management strategies in diabetic kidney disease
Authors: Mao Zi-Hui , Gao Zhong-Xiuzi , Liu Dong-Wei , Liu Zhang-Suo , Wu Peng
Published: January 2023

Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes mellitus and is also one of the serious risk factors in cardiovascular events, end-stage renal disease, and mortality. DKD is associated with the diversified, compositional, and functional alterations of gut microbiota. The interaction between gut microbiota and host is mainly achieved through metabolites, which are small molecules produced by microbial metabolism from exogenous dietary substrates and endogenous host compounds. The gut microbiota plays a critical role in the pathogenesis of DKD by producing multitudinous metabolites. Nevertheless, detailed mechanisms of gut microbiota and its metabolites involved in the occurrence and development of DKD have not been completely elucidated. This review summarizes the specific classes of gut microbiota-derived metabolites, aims to explore the molecular mechanisms of gut microbiota in DKD pathophysiology and progression, recognizes biomarkers for the screening, diagnosis, and prognosis of DKD, as well as provides novel therapeutic strategies for DKD.
Comparing spatial patterns of marine vessels between vessel-tracking data and satellite imagery
Authors: Nakayama Shinnosuke , Dong WenXin , Correro Richard G. , Selig Elizabeth R. , Wabnitz Colette C.C. , Hastie Trevor J. , Leape Jim , Yeung Serena , Micheli Fiorenza
Published: January 2023

Monitoring marine use is essential to effective management but is extremely challenging, particularly where capacity and resources are limited. To overcome these limitations, satellite imagery has emerged as a promising tool for monitoring marine vessel activities that are difficult to observe through publicly available vessel-tracking data. However, the broader use of satellite imagery is hindered by the lack of a clear understanding of where and when it would bring novel information to existing vessel-tracking data. Here, we outline an analytical framework to (1) automatically detect marine vessels in optical satellite imagery using deep learning and (2) statistically contrast geospatial distributions of vessels with the vessel-tracking data. As a proof of concept, we applied our framework to the coastal regions of Peru, where vessels without the Automatic Information System (AIS) are prevalent. Quantifying differences in spatial information between disparate datasets—satellite imagery and vessel-tracking data—offers insight into the biases of each dataset and the potential for additional knowledge through data integration. Our study lays the foundation for understanding how satellite imagery can complement existing vessel-tracking data to improve marine oversight and due diligence.
Performance of Xpert MTB/RIF and sputum microscopy compared to sputum culture for diagnosis of tuberculosis in seven hospitals in Indonesia
Authors: Karuniawati Anis , Burhan Erlina , Koendhori Eko Budi , Sari Desvita , Haryanto Budi , Nuryastuti Titik , Gayatri A. A. A. Yuli , Bahrun Uleng , Kusumawati R. Lia , Sugiyono Retna Indah , Susanto Nugroho Harry , Diana Aly , Kosasih Herman , Naysilla Adhella Menur , Lokida Dewi , Neal Aaron , Siddiqui Sophia , Lau Chuen-Yen , Karyana Muhammad
Published: January 2023

Introduction

Tuberculosis (TB) is a major public health concern in Indonesia, where the incidence was 301 cases per 100,000 inhabitants in 2020 and the prevalence of multi-drug resistant (MDR) TB is increasing. Diagnostic testing approaches vary across Indonesia due to resource limitations. Acid-fast bacilli (AFB) smear is widely used, though Xpert MTB/RIF has been the preferred assay for detecting TB and rifampicin resistance since 2012 due to higher sensitivity and ability to rapidly identify rifampicin resistance. However, <1,000 Xpert instruments were available in Indonesia as of 2020 and the Xpert supply chain has suffered interruptions.

Methods

We compared the performance of Xpert MTB/RIF and AFB smear to facilitate optimization of TB case identification. We analyzed baseline data from a cohort study of adults with pulmonary TB conducted at seven hospitals across Indonesia. We evaluated sensitivity and specificity of AFB smear and Xpert MTB/RIF using Mycobacterium tuberculosis (Mtb) culture as the gold standard, factors associated with assay results, and consistency of Xpert MTB/RIF with drug susceptibility test (DST) in detecting rifampicin resistance.

Results

Sensitivity of AFB smear was significantly lower than Xpert MTB/RIF (86.2 vs. 97.4%, p-value <0.001), but specificity was significantly better (86.7 vs. 73.3%, p-value <0.001). Performance varied by hospital. Positivity rate for AFB smear and Mtb culture was higher in subjects with pulmonary cavities and in morning sputum samples. Consistency of Xpert MTB/RIF with DST was lower in those with rifampicin- sensitive TB by DST.

Discussion

Additional evaluation using sputa from primary and secondary Indonesian health centers will increase the generalizability of the assessment of AFB smear and Xpert MTB/RIF performance, and better inform health policy.

Clinical trial registration

[https://clinicaltrials.gov/], identifier [NCT027 58236].
Further analysis of natural antibodies against ischemic stroke
Authors: Qi Jingjing , Jiang Quanhang , Wang Peng , Wang Zhenqi , Zhang Xuan
Published: January 2023

Background

Our previous study revealed that circulating levels of IgG natural antibodies (NAbs) for vascular endothelial growth factor receptor 1 (VEGFR1) were significantly decreased in patients with arteriosclerosis compared with control subjects. To enhance the sensitivity of an enzyme-linked immunosorbent assay (ELISA) developed in-house for antibody testing, the present work was designed to investigate additive signals in the in-house ELISA developed with the combination of two or more linear peptide antigens derived from target proteins of interest, including VEGFR1, oxidized low-density lipoprotein receptor 1 (LOX-1), interleukins 6 (IL6) and 8 (IL8).

Methods

A total of 218 patients with ischemic stroke and 198 healthy controls were enrolled and an in-house ELISA was developed with linear peptides derived from VEGFR1, LOX-1, IL6, and IL8 to detect their IgG levels in plasma.

Results

Compared with control subjects, plasma levels of IgG NAbs for the IL6-IL8 combination were significantly lower in female patients (Z = −3.149, P = 0.002), whereas male patients showed significantly lower levels of plasma anti-VEGFR IgG (Z = −3.895, P < 0.001) and anti-LOX1a IgG (Z = −4.329, P < 0.001). Because plasma levels of IgG NAbs for both the IL6-IL8-LOX1a-LOX1b combination and the VEGFR1a-VEGFR1b-LOX1a-LOX1b combination were significantly lower in the patient group than the control group, receiver operating characteristic (ROC) analysis was performed and the results showed that the VEGFR1a-VEGFR1b-LOX1a-LOX1b combination had an area under the ROC curve (AUC) of 0.70 for its IgG assay with a sensitivity of 27.1% against the specificity of 95.5% and that the IL6-IL8-LOX1a-LOX1b combination had an AUC of 0.67 for its IgG assay with a sensitivity of 21.1% against the specificity of 95.5%. Spearman correlation analysis showed that plasma IgG NAbs against the IL6-IL8 combination were positively correlated with carotid plaque size only in male patients (r = 0.270, p = 0.002).

Conclusions

Circulating IgG NAbs for the target molecules studied may be potential biomarkers for a subgroup of ischemic stroke and also contribute to the gender differences in clinical presentation of the disease.
Dataset size considerations for robust acoustic and phonetic speech encoding models in EEG
Authors: Desai Maansi , Field Alyssa M. , Hamilton Liberty S.
Published: January 2023

In many experiments that investigate auditory and speech processing in the brain using electroencephalography (EEG), the experimental paradigm is often lengthy and tedious. Typically, the experimenter errs on the side of including more data, more trials, and therefore conducting a longer task to ensure that the data are robust and effects are measurable. Recent studies used naturalistic stimuli to investigate the brain's response to individual or a combination of multiple speech features using system identification techniques, such as multivariate temporal receptive field (mTRF) analyses. The neural data collected from such experiments must be divided into a training set and a test set to fit and validate the mTRF weights. While a good strategy is clearly to collect as much data as is feasible, it is unclear how much data are needed to achieve stable results. Furthermore, it is unclear whether the specific stimulus used for mTRF fitting and the choice of feature representation affects how much data would be required for robust and generalizable results. Here, we used previously collected EEG data from our lab using sentence stimuli and movie stimuli as well as EEG data from an open-source dataset using audiobook stimuli to better understand how much data needs to be collected for naturalistic speech experiments measuring acoustic and phonetic tuning. We found that the EEG receptive field structure tested here stabilizes after collecting a training dataset of approximately 200 s of TIMIT sentences, around 600 s of movie trailers training set data, and approximately 460 s of audiobook training set data. Thus, we provide suggestions on the minimum amount of data that would be necessary for fitting mTRFs from naturalistic listening data. Our findings are motivated by highly practical concerns when working with children, patient populations, or others who may not tolerate long study sessions. These findings will aid future researchers who wish to study naturalistic speech processing in healthy and clinical populations while minimizing participant fatigue and retaining signal quality.
Downregulation of ITGβ3 in colon adenocarcinoma reveals poor prognosis by affecting genome stability, cell cycle, and the tumor immune microenvironment
Authors: Zhao Lei , Ma Xiaoting , Li Guangxin , Zhao Pengfei , Lin Haishan , Ma Yingjie , Li Huihui , Yu Jing
Published: January 2023

Introduction

Abnormal expression of integrin subunit beta 3 (ITGβ3), a gene-encoding protein, is related to the occurrence and development of cancers; however, the biological role of ITGβ3 in colon adenocarcinoma (COAD) remains unclear.

Methods

We used the Cancer Genome Atlas database to obtain the clinical data of patients with COAD, analyzed the mRNA gene clusters related to ITGβ3, and analyzed the interaction signal pathway and interaction protein network of the differentially expressed gene clusters. The results showed that ITGβ3 expression in COAD tumor tissues was significantly downregulated compared with that in paracancerous tissues. Low ITGβ3 expression in tumor tissues is associated with poor overall survival of patients with COAD. In multivariate analysis, stage IV and ITGβ3 low expression were independent prognostic factors. Gene Ontology analysis showed that differentially expressed genes (DEGs) were significantly enriched in leukocyte migration, cell adhesion, and extracellular matrix (ECM) organization. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the DEGs were mainly enriched in ECM-receptor interactions, focal adhesion, and the PI3K-Akt signaling pathway. Protein-protein interaction network analysis revealed the hub and seed genes of the key modules related to ITGβ3. Finally, we analyzed the correlation between TGβ3 and immune-related genes and found that ITGβ3 expression was significantly correlated with tumor purity and infiltration level of dominant immune cells.

Discussion

These findings indicate that ITGβ3 downregulation in COAD may profoundly affect genome stability and multiple steps of the cell cycle, alter the tumor immune microenvironment, and be related to the prognosis of patients with COAD.
Long-term outcomes of nasopharyngeal carcinoma treated with helical tomotherapy using simultaneous integrated boost technique: A 10-year result
Authors: Meng Lingling , Teng Feng , Liu Qiteng , Du Lei , Cai Boning , Xie Chuanbin , Gong Hanshun , Zhang Xinxin , Ma Lin
Published: January 2023

Background

To evaluate the long-term survival and treatment-related toxicities of helical tomotherapy (HT) in nasopharyngeal carcinoma (NPC) patients.

Methods

One hundred and ninety newly diagnosed non-metastatic NPC patients treated with HT from September 2007 to August 2012 were analyzed retrospectively. The dose at D95 prescribed was 70-74Gy, 60-62.7Gy and 52-56Gy delivered in 33 fractions to the primary gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), respectively, using simultaneous integrated boost technique. The statistical analyses were performed and late toxicities were evaluated and scored according to the Common Terminology Criteria for Adverse Events (version 3.0).

Results

The median follow-up time was 145 months. The 10-year local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 94%, 95%, 86%, and 77.8%; respectively. Fifty (26.3%) patients had treatment-related failures at the last follow-up visit. Distant metastasis, occurred in 25 patients, was the major failure pattern. Multivariate analysis showed that age and T stage were independent predictors of DMFS and OS, Concomitant chemotherapy improved overall survival, but anti-EGFR monoclonal antibody therapy failed. The most common late toxicities were mainly graded as 1 or 2.

Conclusions

Helical tomotherapy with simultaneous integrated boost technique offered excellent long-term outcomes for NPC patients, with mild late treatment-related toxicities. Age and clinical stage were independent predictors of DMFS and OS. And, concurrent chemotherapy means better OS. Further prospective study is needed to confirm the superiority of this technology and to evaluate the roles of anti-EGFR monoclonal antibody treatment.
Matrix metalloproteinases as therapeutic targets in breast cancer
Authors: Kwon Mi Jeong
Published: January 2023

Matrix metalloproteinases (MMPs) are the most prominent proteinases involved in tumorigenesis. They were initially recognized to promote tumor progression by remodeling the extracellular matrix through their proteolytic activity. However, accumulating evidence has revealed that some MMPs have protective roles in cancer progression, and the same MMP can exert opposing roles depending on the cell type in which it is expressed or the stage of cancer. Moreover, studies have shown that MMPs are involved in cancer progression through their roles in other biological processes such as cell signaling and immune regulation, independent of their catalytic activity. Despite the prognostic significance of tumoral or stromal expression of MMPs in breast cancer, their roles and molecular mechanisms in breast cancer progression remain unclear. As the failures of early clinical trials with broad-spectrum MMP inhibitors were mainly due to a lack of drug specificity, substantial efforts have been made to develop highly selective MMP inhibitors. Some recently developed MMP inhibitory monoclonal antibodies demonstrated promising anti-tumor effects in preclinical models of breast cancer. Importantly, anti-tumor effects of these antibodies were associated with the modulation of tumor immune microenvironment, suggesting that the use of MMP inhibitors in combination with immunotherapy can improve the efficacy of immunotherapy in HER2-positive or triple-negative breast cancer. In this review, the current understanding of the roles of tumoral or stromal MMPs in breast cancer is summarized, and recent advances in the development of highly selective MMP inhibitors are discussed.
Case report: Histoplasmosis presenting as asymptomatic hypercalcemia detected on routine laboratory testing in a pediatric kidney transplant recipient
Authors: Spiwak Elizabeth , Goswami Shrea , Lay Sara E. , Nailescu Corina
Published: January 2023

Among all infections occurring in pediatric kidney transplant recipients, approximately 1%–5% are fungal. Most fungal infections occur in the first 6 months following kidney transplantation. We present the case of a 15-year-old boy with a history of a kidney transplant 4 years ago, who was found to have asymptomatic moderate hypercalcemia on routine laboratory testing, along with an acute deterioration of his kidney function markers. The cause of his acute kidney injury was likely related to hypercalcemia. An extensive workup for hypercalcemia revealed infection with Histoplasma capsulatum (histoplasmosis) with multiple pulmonary nodules. Hypercalcemia that was initially refractory to medical management resolved after initiating the antifungal treatment. Fungal granulomatous infections such as histoplasmosis should be considered in the differential diagnosis of hypercalcemia in an asymptomatic pediatric kidney transplant recipient.
Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studies
Authors: Chattaraj Bornika , Nandi Arijit , Das Anwesha , Sharma Amit , Dey Yadu Nandan , Kumar Dharmendra , R Mogana
Published: January 2023

The decoction of the whole plant of Enhydra fluctuans is used ethno medicinally by various tribes for the treatment of kidney stones and urinary problems. However, no scientific studies were carried out to delineate its influence on urinary stone formation and crystallisation. Hence, the present study is proposed to investigate the effect of the aqueous extract of Enhydra fluctuans extract on in vitro crystallisation of calcium oxalate. The present study also evaluated. in silico studies of the metabolites with the target proteins present in the renal calcium oxalate stone matrix. The plant material was subjected to decoction to obtain an aqueous extract. The effect of the extract on calcium oxalate crystallization was evaluated by in vitro nucleation and aggregation assays. Further, the metabolites present in E. fluctuans were mined from the existing literature and their number was found to be 35. The selected 35 metabolites of E. fluctuans were subjected to molecular docking with the 5 proteins which are known to be responsible for calcium oxalate crystal growth. Results of in vitro studies indicated that the extract (50, 100, and 200 μg/mL) and standard drug cystone (1,000 μg/mL) exhibited an inhibitory role in the nucleation process where the percentage inhibitions were 52.69, 43.47, 21.98, and 31.67 μg/mL respectively. The results of molecular docking studies revealed that 2 out of 35 metabolites i.e. Baicalein-7-O-diglucoside and 4′,5,6,7-Tetrahydroxy-8-methoxy isoflavone-7-O-beta-D- galactopyranosyl-(1→3)-O-beta-D-xylopyranosyl-(1→4)- O-alpha-L-rhamnopyranoside showed modulatory effects on the four renal stone matrix-associated protein (Human CTP: Phosphoethanolamine Cytidylyltransferase (Protein Data Bank ID: 3ELB), UDP glucose: glycoprotein glucosyltransferase 2 (Gene: UGGT2) (AlphaFold) and RIMS-binding protein 3A (Gene: RIMBP3) (AlphaFold), and Ras GTPase activating-like protein (PDB: 3FAY) based on their docking scores which indicates that they may inhibit the crystallization process. Findings from this study show that Enhydra fluctuans may be effective in the prevention of the crystallization of calcium oxalate. However, further, in vivo studies as well as molecular studies are needed to be conducted to confirm and strengthen its anti-urolithiatic activity and to elucidate the possible mechanism of action involved therein.
Long survival in a pancreatic carcinoma patient with multi-organ toxicities after sintilimab treatment: A case report
Authors: Ni Chen-Xu , Zhao Yu , Qian Hong , Fu Hui , Yan Yu-Ying , Qiu Yu-Shuang , Zhou Can-Can , Huang Fang , Shen Fu-Ming , Li Dong-Jie , Xu Qing
Published: January 2023

Pancreatic carcinoma is the leading cause of death among digestive malignancies in China. In particular, there is no breakthrough in prolonging the survival of pancreatic cancer patients with chemical and targeted therapies. Tumor immunotherapy brings opportunities and progress for the treatment of pancreatic cancer. Sintilimab is an innovative PD-1 inhibitor which was reported certain clinical benefits in multi-line treatments of advanced pancreatic cancer with gemcitabine. The combination therapy of PD-1 with gemcitabine plus high-intensity focused ultrasound (HIFU) in pancreatic cancer has not been reported. Here we report a case of a Chinese old patient diagnosed with metastatic pancreatic cancer. Two months after sintilimab treatment, the patient occurred severe immune colitis. The patient was diagnosed with immune ureteritis after 8 months of treatment. The immue-related adverse events (irAEs) refined after timely recognition and correct intervention by the clinician and clinical pharmacist. After first-line treatment of sintilimab plus gemcitabine combined with pancreatic HIFU, the patient achieved a remarkable benefit of 11-month progression-free survival (PFS) and 20-month overall survival (OS). The first-line treatment of sintilimab plus gemcitabine combined with HIFU demonstrates a potential therapeutic effect on metastatic pancreatic carcinoma with tolerable adverse reactions.
Cholesterol metabolism in the regulation of inflammatory responses
Authors: Bauer Rebekka , Brüne Bernhard , Schmid Tobias
Published: January 2023

The importance of biologically active lipid mediators, such as prostanoids, leukotrienes, and specialized pro-resolving mediators, in the regulation of inflammation is well established. While the relevance of cholesterol in the context of atherosclerosis is also widely accepted, the role of cholesterol and its biosynthetic precursors on inflammatory processes is less comprehensively described. In the present mini-review, we summarize the current understanding of the inflammation-regulatory properties of cholesterol and relevant biosynthetic intermediates taking into account the implications of different subcellular distributions. Finally, we discuss the inflammation-regulatory effect of cholesterol homeostasis in the context of SARS-CoV-2 infections.
Effects of cold water immersion after exercise on fatigue recovery and exercise performance--meta analysis
Authors: Xiao Feiyan , Kabachkova Anastasiia V. , Jiao Lu , Zhao Huan , Kapilevich Leonid V.
Published: January 2023

Cold water immersion (CWI) is very popular as a method reducing post-exercise muscle stiffness, eliminating fatigue, decreasing exercise-induced muscle damage (EIMD), and recovering sports performance. However, there are conflicting opinions as to whether CWI functions positively or negatively. The mechanisms of CWI are still not clear. In this systematic review, we used meta-analysis aims to examine the effect of CWI on fatigue recovery after high-intensity exercise and exercise performance. A total of 20 studies were retrieved and included from PubMed, PEDro and Elsevier databases in this review. Publication years of articles ranged from 2002 to 2022. In selected studies including randomized controlled trials (RCTs) and Crossover design (COD). Analyses of subjective indicators such as delayed-onset muscle soreness (DOMS) and ratings of perceived exertion (RPE), and objective indicators such as countermovement jump (CMJ) and blood plasma markers including creatine kinase(CK), lactate/lactate dehydrogenase(LDH), C-reactive protein(CRP), and IL-6 were performed. Pooled data showed as follows: CWI resulted in a significant decline in subjective characteristics (delayed-onset muscle soreness and perceived exertion at 0 h); CWI reduced countermovement jump(CMJ) significantly at 0 h, creatine kinase(CK) was lowered at 24 h, and lactate at 24 and 48 h. There was no evidence that CWI affects C-reactive protein(CRP) and IL-6 during a 48-h recovery period. Subgroup analysis revealed that different CWI sites and water temperatures have no effect on post-exercise fatigue recovery. Recommended athletes immersed in cold water immediately after exercise, which can effectively reduce muscle soreness and accelerate fatigue recovery.
Evaluation of the mechanism of action of Bacillus spp. to manage Meloidogyne incognita with split root assay, RT-qPCR and qPCR
Authors: Gattoni Kaitlin M. , Park Sang Wook , Lawrence Kathy S.
Published: January 2023

The goal of this research is to determine the mechanism of action of two Bacillus spp. that can manage Meloidogyne incognita population density in cotton. The overall objectives are 1) determine the efficacy and direct antagonistic capabilities of the Bacillus spp. and 2) determine the systemic capabilities of the Bacillus spp. The greenhouse in planta assay indicated B. amyloliquefaciens QST713 and B. firmus I-1582 could manage M. incognita similarly to the chemical standard fluopyram. An in vitro assay determined that B. firmus I-1582 and its extracted metabolites were able to directly manage M. incognita second stage juveniles by increasing mortality rate above 75%. A split root assay, used to determine systemic capabilities of the bacteria, indicated B. amyloliquefaciens QST713 and B. firmus I-1582 could indirectly decrease the nematode population density. Another species, B. mojavensis strain 2, also demonstrated systemic capabilities but was not a successful biological control agent because it supported a high population density in greenhouse in planta assay and in the split root assay. A RT-qPCR assay was used to confirm any systemic activity observed in the split root assay. At 24 hours both B. amyloliquefaciens QST713 and B. firmus I-1582 upregulated one gene involved in the initial stages of JA synthesis pathway but not another gene involved in the later stages of JA synthesis. These results point to a JA intermediate molecule, most likely OPDA, stimulated by the bacteria rather than JA in a short-term systemic response. After 1 week, the Bacillus spp. stimulated a SA-responsive defense related gene. The long-term systemic response to the Bacillus spp. indicates salicylic acid also plays a role in defense conferred by these bacteria. The final assay was a qPCR to determine the concentration of the bacteria on the cotton roots after 24 days. Bacillus amyloliquefaciens QST713 and B. firmus I-43 1582 were able to colonize the root successfully, with the concentration after 24 days not significantly differing from the concentration at inoculation. This study identifies two bacteria that work via systemic resistance and will help aid in implementing these species in an integrated management system.
Metabolomics analysis unveils important changes involved in the salt tolerance of Salicornia europaea
Authors: Duan Huirong , Tiika Richard John , Tian Fuping , Lu Yuan , Zhang Qian , Hu Yu , Cui Guangxin , Yang Hongshan
Published: January 2023

Salicornia europaea is one of the world’s salt-tolerant plant species and is recognized as a model plant for studying the metabolism and molecular mechanisms of halophytes under salinity. To investigate the metabolic responses to salinity stress in S. europaea, this study performed a widely targeted metabolomic analysis after analyzing the physiological characteristics of plants exposed to various NaCl treatments. S. europaea exhibited excellent salt tolerance and could withstand extremely high NaCl concentrations, while lower NaCl conditions (50 and 100 mM) significantly promoted growth by increasing tissue succulence and maintaining a relatively stable K+ concentration. A total of 552 metabolites were detected, 500 of which were differently accumulated, mainly consisting of lipids, organic acids, saccharides, alcohols, amino acids, flavonoids, phenolic acids, and alkaloids. Sucrose, glucose, p-proline, quercetin and its derivatives, and kaempferol derivatives represented core metabolites that are responsive to salinity stress. Glycolysis, flavone and flavonol biosynthesis, and phenylpropanoid biosynthesis were considered as the most important pathways responsible for salt stress response by increasing the osmotic tolerance and antioxidant activities. The high accumulation of some saccharides, flavonoids, and phenolic acids under 50 mM NaCl compared with 300 mM NaCl might contribute to the improved salt tolerance under the 50 mM NaCl treatment. Furthermore, quercetin, quercetin derivatives, and kaempferol derivatives showed varied change patterns in the roots and shoots, while coumaric, caffeic, and ferulic acids increased significantly in the roots, implying that the coping strategies in the shoots and roots varied under salinity stress. These findings lay the foundation for further analysis of the mechanism underlying the response of S. europaea to salinity.
AMMI and GGE biplot analyses of Bambara groundnut [Vigna subterranea (L.) Verdc.] for agronomic performances under three environmental conditions
Authors: Esan Vincent Ishola , Oke Grace Oluwasikemi , Ogunbode Timothy Oyebamiji , Obisesan Idowu Arinola
Published: January 2023

Introduction

The two most common styles to analyze genotype-by-environment interaction (GEI) and estimate genotypes are additive main effects and multiplicative interaction (AMMI) and genotype + genotype × environment (GGE) biplot. Therefore, the aim of this study was to find the winning genotype(s) under three locations, as well as to investigate the nature and extent of GEI effects on Bambara groundnut production.

Methods

The experiment was carried out in the fields of three environments with 15 Bambara groundnut accessions using the randomized complete block design (RCBD) with three replications each in Ibadan, Osun, and Odeda. Yield per plant, fresh seed weight, total number of pods per plant, hundred seed weight, length of seeds, and width of seeds were estimated

Results

According to the combined analysis of variance over environments, genotypes and GEI both had a significant (p < 0.001) impact on Bambara groundnut (BGN) yield. This result revealed that BGN accessions performed differently in the three locations. A two-dimensional GGE biplot was generated using the first two principal component analyses for the pattern of the interaction components with the genotype and GEI. The first two principal component analyses (PCAs) for yield per plant accounted for 59.9% in PCA1 and 40.1% in PCA2. The genotypes that performed best in each environment based on the “which-won-where” polygon were G8, G3, G2, G11, G6, and G4. They were also the vertex genotypes for each environment. Based on the ranking of genotypes, the ideal genotypes were G2 and G6 for YPP, G1 and G5 for FPW, G15 and G13 for TNPP, G3 and GG7 for HSW, G7 and G12 for LOS, and G10 and G7 for WOS. G8 was recorded as the top most-yielding genotype. G8, G4, G7, and G13 were high yielding and the most stable across the environments; G11, G14, and G9 were unstable, but they yielded above-average performance; G14, G12, G15, and G1 were unstable and yielded poorly, as their performances were below average. Bowen was the most discriminating and representative environment and is classified as the superior environment.

Discussion

Based on the performance of accessions in each region, we recommend TVSU 455 (G8) and TVSU 458 (G3) in Bowen, TVSU 455 (G8) and TVSU 939 (G6) and TVSU 454 (G1) in Ibadan, and TVSU 158 (G2) and TVSU 2096 (G10) in Odeda. The variety that performed best in the three environments was TVSU 455 (G8). They could also be used as parental lines in breeding programs.
Exogenous spermidine improved drought tolerance in Ilex verticillata seedlings
Authors: Xie Xiaoting , Gu Yujie , Wang Weili , Abbas Farhat , Qin Sini , Fu Siyi , Mei Jiaqi , Wang Jiayan , Ma Dexuan , Wen Guangchao , Yang Ying , Sharma Anket , Wang Xiaofei , Yan Daoliang , Zheng Bingsong , He Yi , Yuan Huwei
Published: January 2023

Winterberry (Ilex verticillata (L.) A. Gray) is a recently introduced ornamental tree species in China that has not been closely investigated for its drought resistance. In this study, we used two-year-old cuttings from I. verticillata (L.) A. Gray and two representative varieties derived from it, I. verticillata ‘Oosterwijk’ and I. verticillata ‘Jim Dandy’, as materials to investigate how this plant responds to drought stress and whether exogenous spermidine (SPD) can alleviate the negative effects caused by drought stress. The results showed that as the degree of drought stress increased, the leaves of winterberry seedlings became chlorotic, and their edges became dry. Similarly, the relative water content, specific leaf weight, chlorophyll content, leaf nitrogen content, net photosynthetic rate, stomatal conductance and transpiration rate were significantly reduced, whereas the content of malondialdehyde continuously increased with the degree of drought stress. The activities of superoxide dismutase, peroxidase, and catalase increased under moderate drought stress and then decreased under severe drought stress. The levels of soluble sugar and abscisic acid continued to increase, while those of auxin and gibberellic acid decreased. When compared with individual drought stress, an increase in the amount of external SPD clearly alleviated the effect of drought stress on winterberry seedlings. The combined phenotypes and physiological indices of the winterberry leaves under drought stress conditions revealed that the drought resistance of the native species was significantly higher than its two varieties. This finding serves as an important theoretical foundation for the popularization and application of I. verticillata (L.) A. Gray and the two varieties.
Genetic analyses of tropical maize lines under artificial infestation of fall armyworm and foliar diseases under optimum conditions
Authors: Kamweru Isaac , Beyene Yoseph , Bruce Anani Y. , Makumbi Dan , Adetimirin Victor O. , Pérez-Rodríguez Paulino , Toledo Fernando , Crossa Jose , Prasanna Boddupalli M. , Gowda Manje
Published: January 2023

Development and deployment of high-yielding maize varieties with native resistance to Fall armyworm (FAW), turcicum leaf blight (TLB), and gray leaf spot (GLS) infestation is critical for addressing the food insecurity in sub-Saharan Africa. The objectives of this study were to determine the inheritance of resistance for FAW, identity hybrids which in addition to FAW resistance, also show resistance to TLB and GLS, and investigate the usefulness of models based on general combining ability (GCA) and SNP markers in predicting the performance of new untested hybrids. Half-diallel mating scheme was used to generate 105 F1 hybrids from 15 parents and another 55 F1 hybrids from 11 parents. These were evaluated in two experiments, each with commercial checks in multiple locations under FAW artificial infestation and optimum management in Kenya. Under artificial FAW infestation, significant mean squares among hybrids and hybrids x environment were observed for most traits in both experiments, including at least one of the three assessments carried out for foliar damage caused by FAW. Interaction of GCA x environment and specific combining ability (SCA) x environment interactions were significant for all traits under FAW infestation and optimal conditions. Moderate to high heritability estimates were observed for GY under both management conditions. Correlation between GY and two of the three scorings (one and three weeks after infestation) for foliar damage caused by FAW were negative (-0.27 and -0.38) and significant. Positive and significant correlation (0.84) was observed between FAW-inflicted ear damage and the percentage of rotten ears. We identified many superior-performing hybrids compared to the best commercial checks for both GY and FAW resistance associated traits. Inbred lines CML312, CML567, CML488, DTPYC9-F46-1-2-1-2, CKDHL164288, CKDHL166062, and CLRCY039 had significant and positive GCA for GY (positive) and FAW resistance-associated traits (negative). CML567 was a parent in four of the top ten hybrids under optimum and FAW conditions. Both additive and non-additive gene action were important in the inheritance of FAW resistance. Both GCA and marker-based models showed high correlation with field performance, but marker-based models exhibited considerably higher correlation. The best performing hybrids identified in this study could be used as potential single cross testers in the development of three-way FAW resistance hybrids. Overall, our results provide insights that help breeders to design effective breeding strategies to develop FAW resistant hybrids that are high yielding under FAW and optimum conditions.