bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil extracellular traps in relationship to efficacy of systemic therapy for metastatic renal cell carcinoma
Authors: Xie Ruiyang , Shang Bingqing , Shi Hongzhe , Bi Xingang , Song Yan , Qu Wang , Bai Hongsong , Hu Linjun , Wu Jie , Cui Honglei , Du Gan , Guo Lei , Zheng Shan , Ying Jianming , Li Changling , Ma Jianhui , Zhou Aiping , Shou Jianzhong
Published: November 2023

Background

The efficacy of systemic therapy regimens, such as immune checkpoint inhibitors and tyrosine kinase inhibitors (IO‐TKI) and targeted therapy, for metastatic clear cell renal cell carcinoma (ccRCC) remains unpredictable due to the lack of effective biomarkers. Neutrophil extracellular trap (NET) plays an important role in promoting ccRCC. This study explores the NET predictive value of the efficacy in metastatic ccRCC.

Methods

In this retrospective study, patients with metastatic ccRCC who received targeted drugs and IO‐TKI were included. Immunofluorescence staining was utilized to quantify the levels of tissue NETs through cell counts of H3Cit(+) and MPO(+) cells.

Results

A total of 183 patients with metastatic ccRCC were enrolled, including 150 patients who received TKIs and 33 patients who received IO‐TKI. The levels of NETs in tumor tissue were significantly higher than in para‐tumor tissue (p < 0.001). In terms of predicting drug efficacy, a correlation between NET levels and progression‐free survival (PFS) was observed in the TKI with metachronous metastasis group (HR 1.73 [95% CI 1.02–2.91], log‐rank p = 0.037), while no correlation was observed in the TKI with synchronous metastasis group and IO‐TKI group. Regarding overall survival (OS), activated NET levels were associated with poor OS in both TKI (HR 1.60 [95% CI 1.05–2.43], log‐rank p  = 0.017) and IO‐TKI group (HR 4.35 [95% CI 1.06–17.82], log‐rank p =0.047). IMDC score (HR 1.462 [95% CI 1.030–2.075], p = 0.033) and tumor tissue NET levels (HR 1.733 [95% CI 1.165–2.579], p = 0.007) were independent prognostic risk factors for OS in patients with metastatic ccRCC.NET level was associated with poor OS in both TKI (HR 1.60 [95% CI 1.05–2.43], log‐rank p  = 0.017).

Conclusions

The active NET levels in tumor tissue can predict drug efficacy in patients with metastatic ccRCC who received systemic therapy. Elevated levels of NETs in tumor tissue were also associated with poor efficacy in OS.
The value of ATAD3A as a potential biomarker for bladder cancer
Authors: Liu Zhenghong , Sun Li , Zheng Bin , Wang Heng , Qin Xiaowen , Zhang Pu , Wo Qijun , Li Haichang , Mou Yixuan , Zhang Dahong , Wang Shuai
Published: November 2023

Background

Bladder cancer (BCa) is a highly malignant tumor, and if left untreated, it can develop severe hematuria and tumor metastasis, thereby endangering the patient's life. The purpose of this paper was to detect the expression of ATAD3A in BCa and research the relationship between ATAD3A and pathological features of bladder cancer and the prognosis of patients.

Methods

First, the expression of ATAD3A in BCa and normal bladder tissues was analyzed based on the UALCAN and Oncomine public databases. Second, 491 cases of surgically resected bladder cancer specimens and 110 cases of normal adjacent tissues were immunohistochemically stained. The expression of ATAD3A was quantified, and the value and prognosis of ATAD3A as a biomarker of BCa were evaluated.

Results

The expression of ATAD3A in bladder cancer tissues was higher than that in normal bladder mucosa. High expression of ATAD3A was correlated with patient age, tumor size, number of tumors, distant metastasis, lymph node metastasis, lymphovascular invasion, and TNM stage (p < 0.05). Overexpression of ATAD3A is closely related to cancer patient survival. The mean survival time of bladder cancer patients with high ATAD3A expression was shorter than those with low ATAD3A levels. According to the relative comparing result, the high ATAD3A expression herald reduced overall survival in BCa patients.

Conclusions

The abnormal overexpression of ATAD3A may be related to the initiation and progress of bladder cancer. The upregulation of ATAD3A can be used as an effective indicator to diagnose bladder cancer and predict tumor progression. Furthermore, the combination of information from public databases and the results of clinical sample analysis can help us better understand the mechanism of action of molecular oncogenes in bladder cancer.
Identification and Cytotoxic Evaluation of Pregnane Saponins from the Twigs and Leaves of Dregea volubilis
Authors: Diep Vu Thi , Khoa Nguyen Manh , Thu Nguyen Thi , Hien Tran Thi , Tuan Nguyen Hoang , Ha Do Thi
Published: November 2023

Four new polyhydroxy pregnane glycosides, named volubilosides G−K (3, 5–7), along with three known secondary metabolites, dregeoside Da1 (1), dregeoside Ka1 (2), and volubiloside E (4) were isolated from the twigs and leaves of Dregea volubilis (DV). The chemical structures of these compounds (1–7) were elucidated using spectroscopic techniques (1D and 2D NMR and HR‐ESI‐MS analyses) and compared with those in the published literature. Compounds (1–7) were evaluated for cytotoxicity against eight cancer cell lines (MB49, K562, MKN‐7, HT29, A549, MCF‐7, MDA‐MB‐231, and HepG2), revealing varying levels of cytotoxic effects with IC50 values ranging from 4.29 to 21.05 μM. The results indicated that compounds 1–7 may serve as potential lead compounds for the discovery and development of novel anti‐cancer drugs.
Taming the Selective C−H Bond Activation through 1,5‐Palladium Migration
Authors: Fang Yaru , Ding Mingruo , Huang Xueliang
Published: November 2023

“Through space” metal/hydrogen shift constitutes one of the efficient elementary step in organometallic chemistry to achieve selective remote C−H bond functionalization. Compared with the relatively extensive exploration on 1,4‐palladium migration, the processes on corresponding 1,5‐palladium translocation are far less explored. Based on our understanding on related research areas, we summarized the advances achieved in remote C−H bond activation through a key step of 1,5‐palladium migration in this minireview. The background, reaction scope, and more importantly, the mechanistic rationale of each transformation was discussed. We hope by reading through this minireview, one could get a general perspective on direct C−H bond activation via 1,5‐palladium/hydrogen shift, and could understand why such a process is less common when compared with the process going through 1,4‐palladium/hydrogen migration, and eventually could be inspired to develop practical ways for the synthesis of valuable molecules, which could not be prepared easily through other traditional approaches.
First‐Row Transition Metal‐Catalyzed Single Hydroelementation of N‐Heteroarenes
Authors: Park Sehoon
Published: November 2023

Catalytic partial reduction of N‐heteroarenes with H2 or H[E] (E=Si, B‐based) has been a useful and general method for synthesis of a broad range of dihydropyridines (DHP) and dihydroquinolines (DHQ). In recent seven years, one of the most notable advances in this context is being able to utilize earth‐abundant and inexpensive first‐row transition metal‐based catalytic systems. These catalytic procedures are generally considered more environmentally benign and sustainable when compared to conventional catalytic systems relying on precious metals. This Review describes 20 molecular catalytic systems based on first‐row transition metals for selective single hydroelementation of pyridines and quinolines with H2 surrogate, hydrosilanes, and hydroboranes providing 1,2‐ or 1,4‐dihydropyridines and ‐dihydroquinolines. The observed reaction profiles such as scope and activity are briefly presented, while the proposed working modes over a series of elemental steps – H−[E] bond cleavage, hydride (H−) or hydrogen atom (H⋅) transfer, and product release, are discussed in detail on the basis of experimental and/or computational mechanistic observations and insights.
High‐Performance and Stable Polyaniline@Niobium Sulfide Electrode for an Asymmetric Supercapacitor
Authors: Afzal Amir Muhammad , Iqbal Ahmad , Waqas Iqbal Muhammad , Wabaidur Saikh Mohammad , Al-Ammar Essam A. , Mumtaz Sohail , Ha Choi Eun , Abdul Munnaf Shaik
Published: November 2023

Conducting polymers have attained a lot of interest due to extraordinary conductivity, large pore size, and surprising stability. In this work, the conducting polymer polyaniline (PANI) and niobium sulfide (NbS) were synthesized by polymerization of aniline and hydrothermal method, respectively. The PANI@NbS nanocomposite electrode material had a specific capacity (Cs) of 1050 C g−1, which is larger than that of the reference sample (NbS = 300 C g−1). Besides, the hybrid device (PANI@NbS//PANI@AC) was designed and the electrochemical characteristics were determined. The hybrid device showed an excellent value of Cs of 1207 C g−1 with higher energy density Ed and power density Pd. The device also exhibited remarkable stability, and 85 % of the initial capacity is retained after 1000 cycles.
Discovery of Unusual Ajmaline‐Macroline Type Bisindole Alkaloids from Alstonia macrophylla by Building Blocks‐Based Molecular Networking
Authors: Li Zi‐Wei , Fan Chun‐Lin , Sun Biao , Huang Lan , Wang Zi‐Qi , Huang Xiao‐Jun , Zhang Shi‐Qing , Ye Wen‐Cai , Wu Zhen‐Long , Zhang Xiao‐Qi
Published: November 2023

Three unusual ajmaline‐macroline type bisindole alkaloids, alsmaphylines A–C, together with their postulated biogenetic precursors, were isolated from the stem barks and leaves of Alstonia macrophylla via the building blocks‐based molecular network (BBMN) strategy. Alsmaphyline A represents a rare ajmaline‐macroline type bisindole alkaloid with an S‐shape polycyclic ring system. Alsmaphylines B and C are two novel ajmaline‐macroline type bisindole alkaloids with N‐1−C‐21′ linkages, and the former possesses an unconventional stacked conformation due to the presence of intramolecular noncovalent interactions. The chemical structures including absolute configurations of alsmaphylines A–C were established by comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single‐crystal X‐ray crystallography. In addition, a plausible biosynthetic pathway of these bisindole alkaloids as well as their ability to promote the protein synthesis on HT22 cells were discussed.
Hierarchically Porous Covalent Organic Frameworks: Synthesis Methods and Applications
Authors: Wang Xiao , Mu Zhenjie , Shao Pengpeng , Feng Xiao
Published: November 2023

Covalent organic frameworks (COFs) with high porosity have garnered considerable interest for various applications owing to their robust and customizable structure. However, conventional COFs are hindered by their narrow pore size, which poses limitations for applications such as heterogeneous catalysis and guest delivery that typically involve large molecules. The development of hierarchically porous COF (HP‐COF), featuring a multi‐scale aperture distribution, offers a promising solution by significantly enhancing the diffusion capacity and mass transfer for larger molecules. This review focuses on the recent advances in the synthesis strategies of HP‐COF materials, including topological structure design, in‐situ templating, monolithic COF synthesis, defect engineering, and crystalline self‐transformation. The specific operational principles and affecting factors in the synthesis process are summarized and discussed, along with the applications of HP‐COFs in heterogeneous catalysis, toxic component treatment, optoelectronics, and the biomedical field. Overall, this review builds a bridge to understand HP‐COFs and provides guidance for further development of them on synthesis strategies and applications.
An Indacenopicene‐based Buckybowl Catcher for Recognition of Fullerenes
Authors: Scholz Barbara , Oshchepkov Alexander S. , Papaianina Olena , Ruppenstein Cordula , Akhmetov Vladimir A. , Sharapa Dmitry I. , Amsharov Konstantin Y. , Pérez‐Ojeda M. Eugenia
Published: November 2023

Invited for the cover of this issue are the groups of Alexander S. Oshchepkov, Konstantin Y. Amsharov, and M. Eugenia Pérez‐Ojeda at the Max Planck Institute for the Science of Light, Martin‐Luther‐University Halle‐Wittenberg and Friedrich‐Alexander‐Universität Erlangen‐Nürnberg, respectively. The image depicts a buckybowl catcher carefully framing the C70 fullerene which is associated with miraculous, marvellous Fabergé artworks. Read the full text of the article at 10.1002/chem.202302778.
Optimization of purity and yield of amorphous bio‐silica nanoparticles synthesized from bamboo leaves
Authors: Bindar Yazid , Ramli Yusrin , Steven Soen , Restiawaty Elvi
Published: November 2023

The fallen yellowish bamboo leaves around bamboo crops are always overlooked even though they contain high silica in their ash. Bamboo leaf valorization consequently has the potential to be a green process for synthesizing amorphous silica. Unfortunately, the optimum process parameters have not been widely disclosed. Hence, this study intends to optimize the synthesis of amorphous bio‐silica nanoparticles from bamboo leaves using Box–Behnken design (BBD). Bamboo leaves were initially washed with HCl, followed by combustion at 700°C, and then ash washing, extraction of silica with NaOH (sol–gel method), gelation, and drying. According to the results, optimum conditions occur under no acid washing of leaves, solvent‐to‐feed ratio = 5 mL/g, and extraction duration = 1.5 h. The optimum conditions give the highest purity (94.1 wt.%) and yield (42.33%) as well as the highest surface area (328.61 m2/g), smallest pore diameter (8.69 nm), and largest pore volume (0.71 cc/g) of bio‐silica nanoparticles. Furthermore, bio‐silica nanoparticles are amorphous, spherical‐shaped aggregates, and have a white powdered colour.
Supported Atomically Dispersed Pd Catalyzed Direct Alkoxylation and Allylic Alkylation†
Authors: Qin Ruixuan , Chen Ziwen , Wu Qingyuan , Zheng Nanfeng , Liu Pengxin
Published: November 2023

Comprehensive Summary

A new approach to allylic alkylation is realized using an atomically dispersed palladium catalyst (Pd1/TiO2‐EG). Unlike conventional methods that require derivation of substrates and utilization of additives, this method allows for direct allylic alkylation from allylic alcohols, producing H2O as the sole by‐product. The catalyst's high efficiency is attributed to the local hydrogen bonding at the organic‐inorganic interface (Pd‐EG interface), facilitating hydroxyl group activation for η3 π‐allyl complex formation. The system demonstrates successful direct C—O and C—C coupling reactions with high selectivity, requiring no additives. This study highlights the potential of supported atomically dispersed catalysts for greener and more efficient catalysis, meanwhile, offers unique insights into the distinct behavior of atomically dispersed catalysts in comparison to homogeneous or nanoparticle‐based catalysts.
Synthesis of Organofluorine Compounds with Acylsilanes†
Authors: Guo Youyuan , Zhou Gang , Shen Xiao
Published: November 2023

Comprehensive Summary

Organofluorine compounds are central in synthetic chemistry, medicinal chemistry and material chemistry. In this review, we summarize the investigations on the synthesis of organofluorine compounds with acylsilanes. For the non‐fluorinated acylsilanes, the in situ generation of difluoroenoxysilanes from the reactions of the acylsilanes with trifluoromethylation reagents is the major pathway, leading to the facile preparation of various α,α‐difluoroketones. For the fluoroalkylacylsilanes, apart from the in situ generation of difluoroenoxysilanes through anion Brook rearrangement, radical Brook rearrangement of the photoexcited acylsilanes and the selective control of reactivities of the biradicals pave the way for the synthesis of a variety of organofluorine compounds. In general, most of these reactions gave racemic products, and the asymmetric synthesis of organofluorine compounds with acylsilanes is still rare, which would be a future direction of this field.

Key Scientists

In 1957, the first acylsilane compound, triphenylsilyl phenyl ketone was reported by Brook group. In 1991, Portella and coworkers reported the reaction of non‐fluorinated acylsilanes and perfluoroorganometallic reagents without Brook rearrangement, resulting in the formation of alcohols as the products. In 1992, Xu and coworkers carried out the first investigation on fluoroalkylacylsilanes for the preparation of difluoroenoxysilanes through anion Brook rearrangement. In 1994, Portella group reported the synthesis of difluoroenoxysilanes with non‐fluorinated acylsilanes and Ruppert‐Prakash reagent. In 2009, Otaka and coworkers reported a NHC‐mediated intramolecular redox reaction to prepare (Z)‐fluoroalkene dipeptide isosteres (FADIs) from γ,γ‐difluoro‐α,β‐ enoylsilane. Until 2022, the application of radical Brook rearrangement of fluoroalkylacylsilanes for the generation of fluoroalkylsiloxycarbenes was achieved by Shen group, enabling the synthesis of fluoroalkylated cyclopropenols. In 2022, Shen and coworkers successfully achieved the trapping of biradical intermediates generated from fluorine‐containing acylsilanes, leading to the facile preparation of fused gem‐difluorooxetanes. In the same year, Shen group reported the first asymetric reactions of fluoroalkylacylsilanes to prepare enantiomerically enriched fluoroalkyl alcohols and difluoroenoxysilanes.
IKZF3 polymorphisms contribute to the increased risk of acute lymphoblastic leukemia in children
Authors: Yang Xu , Yang Lihua , Luo Annie , Liu Shanshan , Zhang Xiaohong , Liu Xiaoping , Liu Xiaodan , Luo Ailing , Cai Mansi , Yan Yaping , Wu Xuedong , Huang Ke , Xu Ling , Jiang Hua
Published: November 2023

Background

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. IKZF3 (IKAROS family zinc finger 3) is a hematopoietic‐specific transcription factor, and it has been validated that it is involved in leukemia. However, the role of IKZF3 single‐nucleotide polymorphisms (SNPs) remains unclear. In this case–control study, the authors investigated the association of IKZF3 SNPs with ALL in children.

Methods

Six IKZF3 reference SNPs (rs9635726, rs2060941, rs907092, rs12946510, rs1453559, and rs62066988) were genotyped in 692 patients who had ALL (cases) and in 926 controls. The associations between IKZF3 polymorphisms and ALL risk were determined using odds ratios (ORs) and 95% confidence intervals (CIs). The associations of rs9635726 and rs2060941 with the risk of ALL were further estimated by using false‐positive report probability (FPRP) analysis. Functional analysis in silico was performed to evaluate the probability that rs9635726 and rs2060941 might influence the regulation of IKZF3.

Results

The authors observed that rs9635726C>T (adjusted OR, 1.49; 95% CI, 1.06–2.11; p = .023) and rs2060941G>T (adjusted OR, 1.51; 95% CI, 1.24–1.84; p = .001) were related to and increased risk of ALL in the recessive and dominant models, respectively. Furthermore, the associations of both rs9635726 (FPRP = .177) and rs2060941 (FPRP < .001) with ALL were noteworthy in the FPRP analysis. Functional analysis indicated that rs9635726 and rs2060941 might repress the transcription of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21.

Conclusions

This study revealed that IKZF3 polymorphisms were associated with increased ALL susceptibility in children and might influence the expression of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21. IKZF3 polymorphisms were suggested as a biomarker for childhood ALL.
(B, N)‐Rich B−C−N Nanosheet‐assembled Microwires as Effective Electrocatalysts for Oxygen Reduction Reaction
Authors: Cao Lihua , Yang Tao , Mo Haixin , Zhang Yafang , Gao Yongmin , Xu Zhiyong , Kang Bing , Xia Xuefeng , Zhang Wenhua , Xu Zhihao , Xia Fei , Hou Xue
Published: November 2023

Developing highly active and stable nanocarbon electrocatalysts for the oxygen reduction reaction (ORR) in alkaline medium has attracted much attention due to their potential as an alternative to traditional metal‐based or noble metal catalysts. Herein, a unique micro‐nano structure of (B, N)‐rich B−C−N nanosheet‐assembled microwires (BCNNAM) were synthesized and driven electrochemical oxide reduction reaction. The diameter of the microwires about 1 μm, while the nanosheets have an average thickness of less than 20 nm. The compact nanosheets are mostly separated with a bending, curling and crumpling morphology. All those constitutes a ternary system with large surface area and abundant activity sites facilitate fast mass/electron transport for ORR catalytic activity. Thus, the B, N‐rich B−C−N nanosheet‐assembled microwires show significantly improved electrocatalytic activity with an onset potential of 0.95 V and half‐wave potential of 0.83 V compared to BNNAM, nitride‐doped carbon, porous carbon and a commercial Pt/C electrocatalyst. Such high catalytic performance of B, N‐rich B−C−N micro‐nano structures is due to the enhanced activity by the coexistence of B, C and N and the mass transfer promoted by the unique hierarchical porous structure.
Measurement and Mitigation of Bias in Artificial Intelligence: A Narrative Literature Review for Regulatory Science
Authors: Gray Magnus , Samala Ravi , Liu Qi , Skiles Denny , Xu Joshua , Tong Weida , Wu Leihong
Published: November 2023

Artificial intelligence (AI) is increasingly being used in decision making across various industries, including the public health arena. Bias in any decision‐making process can significantly skew outcomes, and AI systems have been shown to exhibit biases at times. The potential for AI systems to perpetuate and even amplify biases is a growing concern. Bias, as used in this paper, refers to the tendency toward a particular characteristic or behavior, and thus, a biased AI system is one that shows biased associations entities. In this literature review, we examine the current state of research on AI bias, including its sources, as well as the methods for measuring, benchmarking, and mitigating it. We also examine the biases and methods of mitigation specifically relevant to the healthcare field and offer a perspective on bias measurement and mitigation in regulatory science decision making.
Evaluation of the serum level of estrogen, progesterone, prolactin, and testosterone in patients with trigeminal neuralgia compared to a healthy population
Authors: Lavaee Fatemeh , Didar Sahar , Afshari Aylar
Published: November 2023

Objectives

The goal of this study is to measure and compare the hormonal serum levels (estrogen, progesterone, testosterone, prolactin, dihydrotestosterone [DHT]) in trigeminal neuroglia (TN) menopausal women and healthy women.

Materials and Methods

This cross‐sectional and case‐control study was performed in 2018 and 2019. For this study, menopausal women with confirmed TN were enrolled. Twenty‐two healthy women in the control group and 19 in the case group participated. Blood samples were taken from participants for assessment of hormonal serum levels (estrogen, progesterone, testosterone, prolactin, DHT). Data were analyzed by SPSS version 18. Mann−Whitney, T‐test, kormography test, nonmetric, χ2 test, and odds ratios have been used.

Results

In patients with TN, the serum level of testosterone was significantly higher (p = .036), and the serum level of prolactin (p = .016) was significantly lower. Other evaluated hormones' serum level was identical in the two groups. Patients with abnormal estrogen levels were more in the TN group in comparison with the healthy group. The abnormality of progesterone in TN patients was more in comparison to the healthy control group.

Conclusions

Estrogen and progesterone serum levels in TN patients are higher in comparison with the healthy group, while prolactin and testosterone serum levels are lower in the control group. Moreover, the DHE serum level is similar in both groups.
Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation
Authors: Stern Lauren , McGuire Helen M , Avdic Selmir , Blyth Emily , Gottlieb David , Patrick Ellis , Abendroth Allison , Slobedman Barry
Published: November 2023

Objectives

Human cytomegalovirus (HCMV) reactivation is the leading viral complication after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Understanding of circulating cytokine/chemokine patterns which accompany HCMV reactivation and correlate with HCMV DNAemia magnitude is limited. We aimed to characterise plasma cytokine/chemokine profiles in 36 allo‐HSCT patients (21 with HCMV reactivation and 15 without HCMV reactivation) at four time‐points in the first 100‐day post‐transplant.

Methods

The concentrations of 31 cytokines/chemokines in plasma samples were analysed using a multiplex bead‐based immunoassay. Cytokine/chemokine concentrations were compared in patients with high‐level HCMV DNAemia, low‐level HCMV DNAemia or no HCMV reactivation, and correlated with immune cell frequencies measured using mass cytometry.

Results

Increased plasma levels of T helper 1‐type cytokines/chemokines (TNF, IL‐18, IP‐10, MIG) were detected in patients with HCMV reactivation at the peak of HCMV DNAemia, relative to non‐reactivators. Stem cell factor (SCF) levels were significantly higher before the detection of HCMV reactivation in patients who went on to develop high‐level HCMV DNAemia (810–52 740 copies/mL) vs. low‐level HCMV DNAemia (< 250 copies/mL). High‐level HCMV reactivators, but not low‐level reactivators, developed an elevated inflammatory cytokine/chemokine profile (MIP‐1α, MIP‐1β, TNF, LT‐α, IL‐13, IL‐9, SCF, HGF) at the peak of reactivation. Plasma cytokine concentrations displayed unique correlations with circulating immune cell frequencies in patients with HCMV reactivation.

Conclusion

This study identifies distinct circulating cytokine/chemokine signatures associated with the magnitude of HCMV DNAemia and the progression of HCMV reactivation after allo‐HSCT, providing important insight into immune recovery patterns associated with HCMV reactivation and viral control.
The spectrum of B cells in the pathogenesis, diagnosis and therapeutic applications of immunoglobulin G4‐related disease
Authors: Hao Qiyuan , Sun Meng , Liu Yanying
Published: November 2023

Immunoglobulin G4 (IgG4)‐related disease is a chronic fibroinflammatory disease mediated by immune disorders. Given the challenging clinical diagnosis and treatment, knowledge of the pathogenesis of IgG4‐related disease is important. The typical elevation of serum IgG4 concentrations and infiltration of IgG4‐positive plasma cells in the involved tissues indicate the involvement of B lymphocytes in the pathogenesis of IgG4‐related disease. Mass production of autoantibodies reflects abnormal activation of B cells, which causes tissue damage. Circulating plasmablasts are recently discovered markers that correlate with serum IgG4 concentration, the extent of organ involvement and disease activity. B‐cell depletion therapy is an emerging curative strategy that can significantly alleviate clinical manifestations and achieve remission in patients with IgG4‐related disease. These findings highlight the potential role of B cells in IgG4‐related disease. In this review, we discuss the pathogenic impact of B lymphocytes on IgG4‐related disease and describe novel therapies targeting B cells.
Investigating the effect of hippocampal sclerosis on parietal memory network
Authors: Ethofer Silke , Milian Monika , Erb Michael , Rona Sabine , Honegger Jürgen , Ethofer Thomas
Published: November 2023

Objective

We aimed to investigate differences in episodic memory networks between patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis and healthy controls, especially with regards to the parietal memory network (PMN), as well as their relation to neuropsychological memory performance after mesial temporal resection.

Methods

28 healthy subjects as well as 21 patients with TLE (12 left, 9 right) were investigated using a spatial memory fMRI paradigm, which has been shown to activate the PMN. Regions of interest (ROI) were defined based on the results of the second‐level analyses and activations within the predefined ROIs were compared across groups and correlated with postoperative verbal and nonverbal memory scores.

Results

Healthy subjects showed activations within regions belonging to the dorsal visual stream and the PMN as well as the bilateral parahippocampal place area, the bilateral frontal eye field, and the bilateral middle frontal gyrus. Comparison between groups revealed that TLE patients activated significantly less in the left middle occipital gyrus and the right precuneus. The activation pattern in left TLE patients showed further reductions, mainly in areas belonging to the dorsal visual stream and the PMN within the left hemisphere. Activations within the left superior parietal lobulus, bilateral inferior parietal lobulus, bilateral middle temporal gyrus, left precuneus, left frontal eye field, and left middle frontal gyrus correlated significantly with postoperative verbal memory scores, and activations within the left superior parietal lobulus, left inferior parietal lobulus, left middle temporal gyrus, and left precuneus correlated significantly with higher performance in postoperative nonverbal memory scores.

Significance

The PMN is involved in episodic memory encoding. Higher activations in areas belonging to the PMN and the dorsal visual stream, especially within the left hemisphere, before amygdalohippocampectomy may result in higher postoperative memory scores.

Plain language summary

This study aims to investigate the effects of epilepsy due to hippocampal sclerosis, i.e. scarring in the temporal lobe, on memory networks in the brain. We discovered that especially patients with left‐sided hippocampal sclerosis show reduced brain activations in visual areas and memory networks within the left hemisphere of the brain during orientation in space. Importantly, higher activations within these areas may result in better memory after epilepsy surgery.
No Effect of Realistic Concentrations of Polyester Microplastic Fibers on Freshwater Zooplankton Communities
Authors: Klasios Natasha , Kim Jihyun O. , Tseng Michelle
Published: November 2023

Zooplankton are a conduit of energy from autotrophic phytoplankton to higher trophic levels, and they can be a primary point of entry of microplastics into the aquatic food chain. Investigating how zooplankton communities are affected by microplastic pollution is thus a key step toward understanding ecosystem-level effects of these global and ubiquitous contaminants. Although the number of studies investigating the biological effects of microplastics has grown exponentially in the last decade, the majority have used controlled laboratory experiments to quantify the impacts of microplastics on individual species. Given that all organisms live in multispecies communities in nature, we used an outdoor 1130-L mesocosm experiment to investigate the effects of microplastic exposure on natural assemblages of zooplankton. We endeavored to simulate an environmentally relevant exposure scenario by manually creating approximately 270 000 0.015 × 1– to 1.5–mm polyester fibers and inoculating mesocosms with zero, low (10 particles/L), and high (50 particles/L) concentrations. We recorded zooplankton abundance and community composition three times throughout the 12-week study. We found no effect of microplastics on zooplankton abundance, Shannon diversity, or Pielou's evenness. Nonmetric multidimensional scaling plots also revealed no effects of microplastics on zooplankton community composition. Our study provides a necessary and realistic baseline on which future studies can build. Because numerous other stressors faced by zooplankton (e.g., food limitation, eutrophication, warming temperatures, pesticides) are likely to exacerbate the effects of microplastics, we caution against concluding that polyester microfibers will always have no effect on zooplankton communities. Instead, we encourage future studies to investigate the triple threats of habitat degradation, climate warming, and microplastic pollution on zooplankton community health. Environ Toxicol Chem 2024;43:418–428. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Investigation on the disaster mechanism and dynamic evolution of a dump slope using experimental and numerical methods: Case study, Kunyang phosphate mine, China
Authors: Li Xiaoshuang , Li Qihang , Hou Guoqing , Zhang Feng , Lu Jun
Published: November 2023

Dump slope is mainly attributed to the deep excavation of a mine. In the present work, the dump in Kunyang phosphate mine located in Sanjia Village was investigated. The geographic and geologic settings were first studied according to the field investigation. Aiming at the actual dump scenario, a rainfall system was designed to simulate the process of dump instability induced by rainfall. The novelty lies in conducting comprehensive tests on fundamental parameters, including water content, particle size, compactness, and engineering mechanical properties, through analogous simulation experiments. In addition, the SLIDE software was adopted to analyse the dumps in each mining area and subsequently determine the sliding disaster mode of the dumps in Kunyang phosphate mine. The comparative analysis of the dumps in these different mining areas showed that the dump in No. 6 mining area has a greater factor of safety (FS) and better stability (instability will not occur). Secondly, the stability of the dumps in No. 2, No. 3 and No. 4 is better than that in No. 5, but they have not reached the ultimate equilibrium state (instability will not occur). Nevertheless, the FS of the dump in No. 1 mining area approached or even fell below 1. Thus, it is predicted that a small‐scale landslide disaster may have occurred (instability). Moreover, the dynamic evolution characteristics of dump disasters with different accumulation densities were revealed by model device tests. Finally, the obvious tube surge phenomenon before sliding was observed.
Is insolvency stigmatised?
Authors: Ghio Emilie , Thomson Donald
Published: November 2023

It is a commonly held belief that there exists a sense of stigma around insolvency, which explains the low uptake of rescue procedures in the United Kingdom and around the world. We assess the accuracy of this claim through two qualitative studies. The first is conducted through interviews with corporate directors in the United Kingdom. The second study is a comparative literature review in selected jurisdictions. The literature review reveals a prominent stigma narrative in policy and legal texts, whereas the interview data reveal only moderate levels of stigma. Rather, they indicate that a lack of knowledge and understanding of insolvency (concept, law and procedures) may be a more powerful factor in explaining why corporate directors do not file for rescue procedures.
Review of optical methods for noninvasive imaging of skin fibroblasts—From in vitro to ex vivo and in vivo visualization
Authors: Nikolaev Viktor V. , Kistenev Yury V. , Kröger Marius , Zuhayri Hala , Darvin Maxim E.
Published: November 2023

Fibroblasts are among the most common cell types in the stroma responsible for creating and maintaining the structural organization of the extracellular matrix in the dermis, skin regeneration, and a range of immune responses. Until now, the processes of fibroblast adaptation and functioning in a varying environment have not been fully understood. Modern laser microscopes are capable of studying fibroblasts in vitro and ex vivo. One‐photon‐ and two‐photon‐excited fluorescence microscopy, Raman spectroscopy/microspectroscopy are well‐suited noninvasive optical methods for fibroblast imaging in vitro and ex vivo. In vivo staining‐free fibroblast imaging is not still implemented. The exception is fibroblast imaging in tattooed skin. Although in vivo noninvasive staining‐free imaging of fibroblasts in the skin has not yet been implemented, it is expected in the future. This review summarizes the state‐of‐the‐art in fibroblast visualization using optical methods and discusses the advantages, limitations, and prospects for future noninvasive imaging.
Shikonin potentiates skin wound healing in Sprague–Dawley rats by stimulating fibroblast and endothelial cell proliferation and angiogenesis
Authors: Xue Chenhong , Dou Jinfa , Zhang Shuzhen , Yu Huiqian , Zhang Shoumin
Published: November 2023

Background

Shikonin, a major component of Lithospermum erythrorhizon, exerts anti‐inflammatory and antibacterial effects and expedites wound healing. This study aims to evaluate the anti‐inflammatory and antioxidant activities of shikonin in a Sprague–Dawley rat model and cell models using fibroblast and endothelial cells.

Methods

The impact of shikonin on the activity of endothelial cells and fibroblasts was examined by cell counting kit 8 and wound‐healing assays. A diabetic rat model was constructed, followed by wound creation for treatment with shikonin. Hematoxylin–eosin staining was used to assess pathological changes, and Masson’s trichrome method to detect collagen deposition. Immunohistochemistry using antibodies against proliferating cell nuclear antigen and CD31 was conducted to detect proliferation and vascular density. Enzyme‐linked immunosorbent assay and immunohistochemistry were carried out to assess pro‐inflammatory and anti‐inflammatory factor concentrations. Western blot and immunofluorescence were implemented to analyze oxidative stress‐related protein expression.

Results

Shikonin induced the activity of both fibroblasts and endothelial cells. Shikonin treatment contributed to facilitated wound healing and higher healing rates in rats. It also resulted in faster lesion debulking in tissues, reduced inflammatory infiltration, increased collagen deposition, and enhanced angiogenesis. Detection of markers at the wounds showed that shikonin accelerated cell proliferation, enhanced tissue remodeling, and inhibited oxidative stress.

Conclusion

Shikonin stimulates the proliferation and migration of fibroblasts and endothelial cells to promote angiogenesis and tissue remodeling, resulting in faster wound healing.
The trabecular architecture of the popliteal sesamoid bone (cyamella) from a New Zealand white rabbit (Oryctolagus cuniculus)
Authors: Barak Meir M.
Published: November 2023

Sesamoid bones are ossified structures that are embedded in tendons near articulation. They consist of an inner trabecular bone architecture surrounded by a thin cortical shell. While the formation of sesamoid bones is probably mainly controlled by genetic factors, the proper development and mineralization of a sesamoid bone depends also on mechanical stimulation. While most sesamoid bones are not loaded directly by other bones during locomotion, they still experience forces directed from the tendon in which they are embedded. In cases when the sesamoid bone is experiencing forces only from a single tendon, such as the cyamella in the rabbit, this may give us a tool to study bone functional adaptation in a relatively simple loading setting. This study investigates the internal trabecular architecture of the popliteal sesamoid bone (cyamellae) in New Zealand white (NZW) rabbits (Oryctolagus cuniculus). Five hind limbs of NZW rabbits were micro‐computed tomography scanned and the cortical and trabecular architectures of the cyamellae were evaluated. The results revealed that similar to the patella, the cyamella has a thin cortex and a high trabecular bone volume fraction (BV/TV), which is derived mostly from the high trabecular thickness (Tb.Th). Trabecular BV/TV and Tb.Th were not distributed homogeneously, but they were lower at the periphery and higher closer to the proximal and middle of the cyamella, near the musculotendinous junction. The results also demonstrated that trabeculae tend to align along two recognizable orientations, one with the direction of tensile stresses, in line with the popliteal tendon, and the second bridging the narrow space between the cranial and caudal cortical faces of the bone.
SPOP inhibits HBV transcription and replication by ubiquitination and degradation of HNF1α
Authors: Pi Yubo , Li Yang , Yan Qi , Luo Huimin , Zhou Peng , Chang Wenyi , Gong Deao , Hu Yuan , Wang Kai , Tang Ni , Huang Ailong , Chen Yanmeng
Published: November 2023

Hepatitis B virus (HBV) infection remains a significant public health burden worldwide. The persistence of covalently closed circular DNA (cccDNA) within the nucleus of infected hepatocytes is responsible for the failure of antiviral treatments. The ubiquitin proteasome system (UPS) has emerged as a promising antiviral target, as it can regulate HBV replication by promoting critical protein degradation in steps of viral life cycle. Speckle‐type POZ protein (SPOP) is a critical adaptor for Cul3‐RBX1 E3 ubiquitin ligase complex, but the effect of SPOP on HBV replication is less known. Here, we identified SPOP as a novel host antiviral factor against HBV infection. SPOP overexpression significantly inhibited the transcriptional activity of HBV cccDNA without affecting cccDNA level in HBV‐infected HepG2‐NTCP and primary human hepatocyte cells. Mechanism studies showed that SPOP interacted with hepatocyte nuclear factor 1α (HNF1α), and induced HNF1α degradation through host UPS pathway. Moreover, the antiviral role of SPOP was also confirmed in vivo. Together, our findings reveal that SPOP is a novel host factor which inhibits HBV transcription and replication by ubiquitination and degradation of HNF1α, providing a potential therapeutic strategy for the treatment of HBV infection.
Temporal and spatial variations of multivariate hot, dry and windy climate extremes in Northwest China
Authors: Feng Yao , Sun Fubao , Liu Fa
Published: November 2023

The simultaneous occurrence of extreme weather events such as high temperature, low humidity and strong wind speed can cause devastating impacts on the fragile environment and vulnerable ecosystem in arid Northwest China (NW). However, few studies investigate the multivariate compound hot, dry and windy extremes in NW. In this study, we investigate the temporal and spatial variations of the warm‐season trivariate hot, dry and windy (HDW) and bivariate hot and dry (HD), dry and windy (DW), hot and windy (HW) extremes in NW. From 1960 to 2019, we observed more compound HD, DW, HW and HDW days in the hyper‐arid Xinjiang and west Gansu in NW. Simultaneously, DW days, HW days and HDW days consistently declined at rates of −0.48, −0.88 and −0.42 day·10a−1, except for a discernible increasing rate of 0.56 day·10a−1 in HD days. Notably, trends in four multivariate compound extremes all experienced pronounced reversals from a declining to increasing trend in the 1990s. The higher probability of compound HD, DW and HW extremes contributed to a higher probability of HDW in Xinjiang province. Ultimately driven by the significantly rising temperature (0.21°C·10a−1, p < 0.01), four compound extremes suggested increased probability with the largest increase in compound HW probability from 1960–1989 to 1990–2019. Both the rising trends in the occurrence and the increased probability of four compound extremes highlight intense risks of compound extreme weather over NW in recent decades.
Rapid terrace incision and Quaternary landscape evolution in central Patagonia
Authors: Thorndycraft Varyl Robert
Published: November 2023

The debate over isostatic uplift versus discharge as drivers of Quaternary river incision is explored here through geospatial analysis of a ~250‐m‐relief terrace sequence from the Río Pinturas (Argentine Patagonia). The geomorphic setting of the Cañadon Caracoles reach allows evaluation of discharge as a driver of terrace incision because advancing ice during Pleistocene glaciations blocked Pacific drainage and routed meltwater from an expanded ~104‐km2 catchment to the Atlantic through the dryland steppe of the study area. Twenty‐two terrace levels, some assigned to previously dated ice margins [Marine Isotope Stage (MIS) 32–36, MIS 16, MIS 8 and MIS 2], were identified. Average net incision since 800 ka (~0.34 m ka−1) exceeded regional uplift rates. The MIS 2 terraces, with ante quem and post quem age constraint on the timing of terrace formation, show that terrace incision was episodic and faster still during a transitional warming climate. Glacier recession and proglacial lake formation at ~18 ka led to rapid incision of ~11.7 m ka−1 over a few millennia. River capture and negligible flow from ~15.0 ka caused fan‐dammed lake formation on the valley floor and vertical stability during MIS 1. The Pinturas terraces demonstrate rapid incision can be driven by discharge and sediment dynamics.
Maternal folic acid and vitaminB12supplementation during medium to late gestation promotes fetal development via improving placental antioxidant capacity, angiogenesis and amino acid transport
Authors: Zhou Rui , Zhe Li , Chen Fangyuan , Gao Tianle , Zhang Xiaoling , Huang Lingjie , Zhuo Yong , Xu Shengyu , Lin Yan , Feng Bin , Che Lianqiang , Wu De , Fang Zhengfeng
Published: November 2023

BACKGROUND

Folic acid and vitamin B12(FV), being B vitamins, not only facilitate the remethylation of homocysteine (Hcy) but also contribute to embryonic development. This study aimed to assess the impact of FV supplementation during late pregnancy on sows' reproductive performance, amino acid metabolism, placental angiogenesis, and related parameters. Twenty primiparous sows at day 60 of gestation were randomly allocated to two groups: a basal diet (CON) group and a group receiving a basal diet supplemented with folic acid at 20 ppm and vitamin B12at 125 ppb.

RESULTS

The findings revealed that dietary FV supplementation significantly reduced the incidence of intrauterine growth retardation compared to the CON group (P < 0.05). Furthermore, it led to a decrease in the Hcy levels in umbilical cord serum (P < 0.05) and activation of the placental mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway (P < 0.05). Additionally, FV supplementation lowered placental malondialdehyde levels (P < 0.05) and increased the expression of placental thioredoxin (P = 0.05). Moreover, maternal FV supplementation notably elevated placental vascular density (P < 0.05) and the expression of sodium‐coupled neutral amino acid transporter 2 (SNAT2) (P < 0.05), as well as amino acid concentrations in umbilical cord blood (P < 0.05).

CONCLUSION

Maternal FV supplementation during medium to late gestation reduced Hcy levels in umbilical cord blood and positively impacted fetal development. This improvement was closely associated with increased placental antioxidant capacity and vascular density, as well as activation of the placental mTORC1‐SNAT2 signaling pathway. © 2023 Society of Chemical Industry.
Safety and efficacy of intracranial vascularized submental lymph node transfer for treating hydrocephalus
Authors: Wu Robin , Lu Yu‐Jen , Ro Long‐Sun , Hsu Jung‐Lung , Cheng Ming‐Huei
Published: November 2023

Hydrocephalus is routinely treated with ventriculoperitoneal shunt drainage of cerebrospinal fluid (CSF), a procedure plagued by high morbidity and frequent revisions. Vascularized submental lymph node (VSLN) transplants act as lymphatic pumps to drain interstitial fluid (ISF) from lymphedematous extremities. As the field of neuro‐lymphatics comes to fruition, we hypothesize the efficacy of VSLN in the drainage of intracranial CSF‐ISF. We report novel placement of VSLN in the temporal subdural space in two patients diagnosed with symptomatic communicating hydrocephalus. At a minimum follow‐up of 1 month postoperatively, both experienced radiological and clinical improvements.