bluuebunny/crossref_metadata_2025 huggingface dataset:
Reviewing the evolutive ACQ‐to‐AIE transformation of photosensitizers for phototheranostics
Authors: Zhu Wei , Huang Lin , Wu Chao , Liu Lingli , Li Haoxuan
Published: December 2023

Photodynamic therapy (PDT) represents an emerging noninvasive treatment technique for cancers and various nonmalignant diseases, including infections. During the process of PDT, the physical and chemical properties of photosensitizers (PSs) critically determine the effectiveness of PDT. Traditional PSs have made great progress in clinical applications. One of the challenges is that traditional PSs suffer from aggregation‐caused quenching (ACQ) due to their discotic structures. Recently, aggregation‐induced emission PSs (AIE‐PSs) with a twisted propeller‐shaped conformation have been widely concerned because of high reactive oxygen species (ROS) generation efficiency, strong fluorescence efficiency, and resistance to photobleaching. However, AIE‐PSs also have some disadvantages, such as short absorption wavelengths and insufficient molar absorption coefficient. When the advantages and disadvantages of AIE‐PSs and ACQ‐PSs are complementary, combining ACQ‐PSs and AIE‐PSs is a “win‐to‐win” strategy. As far as we know, the conversion of traditional representative ACQ‐PSs to AIE‐PSs for phototheranostics has not been reviewed. In the review, we summarize the recent progress on the ACQ‐to‐AIE transformation of PSs and the strategies to achieve desirable theranostic applications. The review would be helpful to design more efficient ACQ‐AIE‐PSs in the future and to accelerate the development and clinical application of PDT.
Precise ligand engineering of Ir(III)‐based photosensitizer with aggregation‐induced emission for image‐guided photodynamic therapy
Authors: Tong Jialin , Liu Ao , Huang Shanshan , Zhou Dan , Gao Ying , Wang Yan , Shan Guo‐Gang
Published: December 2023

Photodynamic therapy (PDT), which relies on the production of reactive oxygen species (ROS) induced by a photosensitizer to kill cancer cells, has become a non‐invasive approach to combat cancer. However, the conventional aggregation‐caused quenching effect, as well as the low ROS generation ability of photosensitizers, restrict their biological applications. In this work, a new Ir(III) complex with a dendritic ligand has been strategically designed and synthesized by ingenious modification of the ancillary ligand of a reported Ir(III) complex (Ir‐1). The extended π‐conjugation and multiple aromatic donor moieties endow the resulting complex Ir‐2 with obvious aggregation‐induced emission (AIE) activity and bathochromic emission. In in vitro experiments, importantly, Ir‐2 nanoparticles exhibit the excellent photoinduced ROS generation capabilities of O2•− and 1O2, as well as excellent biocompatibility and the lipid droplets (LDs) targeting feature. This study would provide useful guidance to design efficient Ir(III)‐based photosensitizers used in biological applications in the future.
Impact of ligand environment on optical, luminescence and thermometric behavior of A3(PO4)2:Sm3+ (A = Ca, Sr) phosphors
Authors: Singh Rajan , Manhas Mohit , Bedyal Ankush Kumar , Durani Fahim , Swart Hendrick C. , Kumar Vinay
Published: December 2023

The present study investigates the impact of the ligand environment on the luminescence and thermometric behavior of Sm3+ doped A3(PO4)2 (A = Sr, Ca) phosphors prepared by combustion synthesis. The structural and luminescent properties of Sm3+ ions in the phosphate lattices were investigated using powder X‐ray diffraction (PXRD) and photoluminescence (PL) techniques. PXRD results of the synthesized phosphors exhibit the expected phases that are in agreement with their respective standards. Fourier‐transform infrared (FTIR) spectroscopy confirms the presence of PO4 vibrational bands. Upon excitation with near ultraviolet light, the PL studies indicated that Sr3(PO4)2:Sm3+ phosphors exhibit a yellow light emission, whereas Ca3(PO4)2:Sm3+ phosphors exhibit an emission of orange light. The PL emission results are in accordance with the CIE coordinates, with the Sr3(PO4)2:Sm3+ phosphors showing coordinates of (0.56, 0.44), and the Ca3(PO4)2:Sm3+ phosphors displaying coordinates of (0.60, 0.40). Thermal analysis shows improved stability of Ca3(PO4)2:Sm3+ based on lower weight reduction in thermogravimetric analysis. The effect of temperature on the luminescence properties of the phosphor has been examined upon a 405 nm excitation. By using the fluorescence intensity ratio (FIR) method, the temperature responses of the emission ratios from the Sm3+: the 4F3/2 → 6H5/2 transition to the 4G5/2 → 6H7/2 and 4F3/2 → 6H5/2 transition to the 4G5/2 → 6H9/2 emissions are characterized. The Ca3(PO4)2:Sm3+ phosphors are more sensitive as compared with the Sr3(PO4)2:Sm3+ phosphors. The earlier research findings strongly indicate that these phosphors hold great promise as ideal candidates for applications in non‐invasive optical thermometry and solid‐state lighting devices.
Development and validation of a liquid chromatography–tandem mass spectrometry method for the quantification of the acetyl‐coenzyme A competitive p300/CBP catalytic inhibitor A‐485 in biological samples
Authors: Oertel Reinhard , Jaschke Nikolai , Lippert Annemarie , Renner Bertold
Published: December 2023

The small molecule A‐485 competitively inhibits the histone acetyltransferase domain of CBP (cyclic‐adenosine monophosphate response element‐binding protein)/p300. Apart from its antineoplastic activity, researchers are exploring its potential benefits in treating osteoporosis and its impact on energy metabolism. However, so far, only limited pharmacokinetic data are available, and the crucial determination of A‐485 concentration in various biological materials with small sample volumes remains unpublished. A rapid and sensitive LC–tandem mass spectrometry method has been developed and validated to quantify A‐485 in mouse serum and tissue. In this method, serum samples underwent precipitation with acetonitrile, while cell lysates were appropriately diluted. The determination of A‐485 utilized a reversed‐phase column with a mobile phase gradient, and detection was carried out in multiple reaction monitoring mode. The lower standard sample, with a concentration of 7.8 ng/mL, served as the lower limit of quantification, while the upper standard was established at 1000 ng/mL. A‐485 concentrations were assessed in both serum samples and the lysate of all examined tissues, revealing swift metabolic clearance. The analytical method outlined here is deemed appropriate for subsequent studies. The ability to measure the active ingredient in various compartments facilitates the determination of accurate pharmacokinetic parameters. In the event of human use of A‐485, the analysis method can be seamlessly transferred to human samples.
The nomogram for the prediction of overall survival after surgery in patients in early‐stage NSCLC based on SEER database and external validation cohort
Authors: Zhang Hao , Zeng Jingtong , Li Xianjie , Zhang Bo , Wang Hanqing , Tang Quanying , Zhang Yifan , Bao Shihao , Zu Lingling , Xu Xiaohong , Xu Song , Song Zuoqing
Published: December 2023

Background & Aims

Currently, there is a lack of effective tools for predicting the prognostic outcome of early‐stage lung cancer after surgery. We aim to create a nomogram model to help clinicians assess the risk of postoperative recurrence or metastasis.

Materials and Methods

This work obtained 16,459 NSCLC patients based on SEER database from 2010 to 2015. In addition, we also enrolled 385 NSCLC patients (2017/01‐2019/06) into external validation cohort at Tianjin Medical University General Hospital. Univariable as well as multivariable Cox regression was carried out for identifying factors independently predicting OS. In addition, we built a nomogram by incorporating the above prognostic factors for the prediction of OS.

Results

Tumor size was positively correlated with the risk of poor differentiation. Advanced age, male and adenocarcinoma patients were factors independently predicting poor prognosis. The risk of white race is higher, followed by Black race, Asians and Indians, which is consistent with previous study. Chemotherapy is negatively related to prognostic outcome in patients of Stage IA NSCLC and positively related to that in those of Stage IB NSCLC. Lymph node dissection can reduce the postoperative mortality of patients. AUCs of the nomograms for 1, 2, and 3‐year OS was 0.705, 0.712, and 0.714 for training cohort, while those were 0.684, 0.688, and 0.688 for validation cohort.

Conclusions

The nomogram could be used as a tool to predict the postoperative prognosis of patients with Stage I non‐small cell lung cancer.
Long‐term outcomes of metastasis‐directed stereotactic body radiation therapy in metastatic nasopharyngeal carcinoma
Authors: Yang Jiangping , Liao Wenjun , Su Shitong , Zeng Ni , Zhang Shichuan , He Jinlan , Chen Nianyong
Published: December 2023

Background

The study aims to evaluate the outcomes of metastasis‐directed stereotactic body radiation therapy (SBRT) in metastatic nasopharyngeal carcinoma (mNPC).

Methods

We reviewed all SBRT conducted in patients with mNPC in our institution between 2013 and 2022. Systemic therapy was performed with chemotherapy with or without anti‐programmed death‐1 (PD‐1) therapy. Local treatment delivered with ablative purpose in stereotactic setting with dose/fraction ≥5 Gy was evaluated. Kaplan–Meier analyses were used to determine the rates of local control (LC), progression‐free survival (PFS), and overall survival (OS). Univariate and multivariate analyses were performed by Cox regression.

Results

A total of 54 patients with 76 metastatic sites receiving SBRT were analyzed. Median follow‐up was 49 months. The 3‐year LC, PFS, and OS rates were 89.1%, 29.4%, and 57.9%, respectively. Adding a PD‐1 inhibitor to SBRT tended to prolong median OS (50.1 vs. 32.2 months, p = 0.068). Patients receiving a biological effective dose (BED, α/β = 10) ≥ 80 Gy had a significantly longer median OS compared to those who received a lower dose (not reached vs. 29.5 months, p = 0.004). Patients with oligometastases (1–5 metastases) had a better median OS (not reached vs. 29.5 months, p < 0.001) and PFS (34.3 vs. 4.6 months, p < 0.001). Pretreatment EBV‐DNA and maintenance therapy were also significant predictors for OS.

Conclusions

Metastatic NPC patients could benefit from metastases‐directed SBRT in combination with systemic therapy.
Design and Synthesis of Pyrazole Carboxamide Derivatives as Selective Cholinesterase and Carbonic Anhydrase Inhibitors: Molecular Docking and Biological Evaluation
Authors: Durgun Mustafa , Akocak Suleyman , Lolak Nebih , Topal Fevzi , Koçyiğit Ümit Muhammet , Türkeş Cüneyt , Işık Mesut , Beydemir Şükrü
Published: December 2023

The present study focused on the synthesis and characterization of novel pyrazole carboxamide derivatives (SA1‐12). The inhibitory effect of the compounds on cholinesterases (ChEs; AChE and BChE) and carbonic anhydrases (hCAs; hCA I and hCA II) isoenzymes were screened as in vitro. These series compounds have been identified as potential inhibitors with a KI values in the range of 10.69±1.27–70.87±8.11 nM for hCA I, 20.01±3.48–56.63±6.41 nM for hCA II, 6.60±0.62‐14.15±1.09 nM for acetylcholinesterase (AChE) and 54.87±7.76–137.20 ±9.61 nM for butyrylcholinesterase (BChE). These compounds have a more effective inhibition effect when compared to the reference compounds. In addition, the potential binding positions of the compounds with high affinity for ChE and hCAs were demonstrated by in silico methods. The results of in silico and in vitro studies support each other. As a result of the present study, the compounds with high inhibitory activity for metabolic enzymes, such as ChE and hCA were designed. The compounds may be potential alternative agents used as selective ChE and hCA inhibitors in the treatment of Alzheimer′s disease and glaucoma.
Optimal decisions under price dynamics for Roth conversions
Authors: DiLellio James A. , Goldfeder Philip M. , McQuarrie Edward F.
Published: December 2023

Retirees are faced with a variety of choices during their working and retirement years on how to best support their retirement lifestyle and estate planning goals. One of these choices is the option to convert a portion of their pretax savings from a tax‐deferred account (TDA) into a tax‐exempt Roth account. In this article, we quantify the Roth conversion payoff and when/how it depends on investment returns. We show that, while the use of taxable account assets may produce a larger payoff than early withdrawals from the Roth IRA, large unrealized taxable account gains and estate plans may change this calculus. Our work provides a recommendation on how current dividends or cash versus appreciated assets should be used to optimize Roth conversion payoffs, and informs FinTech companies and robo‐advisors on how to best support this important option for millions of current and future retirees.
Label‐Free Detection of Unbound Bilirubin and Nitrophenol Explosives in Water by a Mechanosynthesized Dual Functional Zinc Complex: Recognition of Picric Acid in Various Common Organic Media
Authors: Nair Ratish R. , Debnath Snehasish , Ghosh Riya , Bhattacharya Arnab , Raju M. , Chatterjee Pabitra B.
Published: December 2023

High levels of unconjugated bilirubin (UB) in serum lead to asymptomatic and neonatal jaundice and brain dysfunctions. Herein, we have reported the detection of UB at as low as 1 μM in an aqueous alkaline medium using a Zn(II) complex. The specificity of the complex has been validated by the HPLC in the concentration window 6–90 μM, which is rare. The sensory response of the probe at physiological pH against nitro explosives developed it as an instant‐acting fluorosensor for picric acid (PA) and 2,4‐dinitrophenol (2,4‐DNP). Spectroscopic titration provided a binding constant of 4×105 M−1 with PA. The naked eye detection was found to be 15 μM. The solid‐state photoluminescent nature of the complex enabled it for PA sensing in the solid phase. Interestingly, the probe remained fluorescent in various volatile and non‐volatile organic solvents. As a result, it can also detect PA and 2,4‐DNP in a wide range of common organic media. NMR studies revealed the coordination of PA, 2,4‐DNP, and UB to the Zn(II) center of the probe, which is responsible for the observed quenching of the probe with the analytes.
Cu(I) Complexes Comprising tetrahedral Mo2E2 or Mo2PE units (E=P, As, Sb) as Chelating Ligands
Authors: Mondal Bijan , Scheer Manfred
Published: December 2023

Novel isomorphous tetranuclear complexes, [(dppf)Cu(μ3,η2 : 2 : 2‐E2{CpMo(CO)2}2]BF4 [E=P (1), As (4), Sb (5), (dppf=1,1′‐bis‐(diphenylphosphino)‐ferrocene)] and [(dppf)Cu(μ3,η2 : 2 : 2‐PE{CpMo(CO)2}2]BF4 [E=As (2), Sb(3)] were synthesized from the reactions between [(dppf)Cu(MeCN)2][BF4] and tetrahedral molybdenum complexes containing unsubstituted homo‐ and hetero‐diatomic group‐15 elements [(μ,η2 : 2‐E2{CpMo(CO)2}2] [E=P (A), As (D), Sb (E)] and [(μ,η2 : 2‐PE{CpMo(CO)2}2] [E=As (B), Sb (C)], respectively. In all these products, the {Mo2E2} or {Mo2PE} moieties coordinate the Cu(I) center via a rare side‐on η2‐coordination mode. The X‐ray structure analyses of [(dppf)Cu(μ3,η2 : 2 : 1‐PSb{CpMo(CO)2}2][BF4] demonstrate, for the first time, the utilization of an η1‐coordination mode for the ligand complex C to coordinate to the Cu(I) center. All the products were characterized by X‐ray crystallography, NMR and IR spectroscopy, mass spectrometry and elemental analysis. Electrochemical studies also revealed the formation of 1–5, and, further, to understand the structure and bonding of the products, theoretical calculations using density functional theory (DFT) were conducted.
Bicyclo[m.n.k]alkane Building Blocks as Promising Benzene and Cycloalkane Isosteres: Multigram Synthesis, Physicochemical and Structural Characterization
Authors: Semeno Volodymyr V. , Vasylchenko Vadym O. , Fesun Ihor M. , Ruzhylo Liudmyla Yu. , Kipriianov Mykhailo O. , Melnykov Kostiantyn P. , Skreminskyi Artem , Iminov Rustam , Mykhailiuk Pavel , Vashchenko Bohdan V. , Grygorenko Oleksandr O.
Published: December 2023

Electrophilic double bond functionalization – intramolecular enolate alkylation sequence was used to obtain a series of bridged and fused bicyclo[m.n.k]alkane derivatives (i. e., bicyclo[4.1.1]octanes, bicyclo[2.2.1]heptanes, bicyclo[3.2.1]octanes, bicyclo[3.1.0]hexanes, and bicyclo[4.2.0]heptanes). The scope and limitations of the method were established, and applicability to the multigram synthesis of target bicyclic compounds was illustrated. Using the developed protocols, over 50 mono‐ and bifunctional building blocks relevant to medicinal chemistry were prepared. The synthesized compounds are promising isosteres of benzene and cycloalkane rings, which is confirmed by their physicochemical and structural characterization (pKa, LogP, and exit vector parameters (EVP)). “Rules of thumb” for the upcoming isosteric replacement studies were proposed.
How subjective ethical congruence facilitates leadership identification construction: A followership perspective
Authors: Fan Wei , Wang Zhenyuan , Wang Wen
Published: December 2023

This study examines subordinate subjective congruence resulting from personal ethical identity and perceived ethical leadership (PEL) on followership behaviors, including: obedience, proactive, and constructive resistance behaviors through identification with supervisors. Using polynomial regressions, results from self‐reported data of 208 employees in China supported that higher level of identification with supervisor occurs because of the following: (1) ethical congruence rather than ethical incongruence; (2) high‐high rather than low‐low congruence; (3) incongruence when personal ethical identity is lower than PEL rather than when personal ethical identity is higher than PEL. Moreover, such perceived ethical congruence facilitates followership obedience and proactive behaviors but not constructive resistance behavior via identification with supervisors. Relevant theoretical and practical implications are discussed.
A Label‐Free Deoxyribozyme Sensor for m6A Demethylase Activity Detection†
Authors: Wang Xiuyuan , Yu Shusheng , He Yuqiu , Wang Fuan , Liu Xiaoqing
Published: December 2023

Comprehensive Summary

A label‐free deoxyribozyme (DNAzyme) biosensor for m6A demethylase activity detection is developed. When demethylase FTO (Fat mass and obesity‐associated protein), an important m6A demethylase of ALKBH demethylase family is present, the m6A group is specifically demethylated, and the cleavage activity of DNAzyme is restored. This allows the cleavage product that contains G‐quadruplex sequence to bind to thioflavin T (ThT) and generate fluorescence signals. The biosensor shows high specificity and sensitivity, and fast reaction speed. Our study demonstrates a new design of allosteric DNAzyme for sensing. This method represents the first label‐free nucleic acid biosensor for FTO assay, providing a feasible route towards inhibitors screening.
Longitudinal adherence to annual colorectal cancer screening among Black persons living in the United States enrolled in a community‐based randomized trial
Authors: Arevalo Mariana , Sutton Steven K. , Abdulla Rania , Christy Shannon M. , Meade Cathy D. , Roetzheim Richard G. , Gwede Clement K.
Published: December 2023

Background

This study examined repeat colorectal cancer screening rates at 12 and 24 months as part of a randomized intervention trial among Black persons living in the United States and factors associated with screening adherence.

Methods

Participants completed a survey assessing demographics and Preventive Health Model (PHM) factors (e.g., self efficacy, susceptibility) and received either a culturally targeted photonovella plus free fecal immunochemical test (FIT) kits (intervention group) or a standard educational brochure plus free FIT kits (comparison group). FIT return was assessed at 6, 12, and 24 months. Descriptive statistics summarized patterns of repeat screening. Logistic regression models assessed FIT uptake overtime, and demographic and PHM factors associated with screening adherence.

Results

Participants (N = 330) were U.S.‐born (93%), non‐Hispanic (97%), and male (52%). Initial FIT uptake within 6 months of enrollment was 86.6%, and subsequently dropped to 54.5% at 12 months and 36.6% at 24 months. Higher FIT return rates were observed for the brochure group at 24 months (51.5% vs 33.3% photonovella, p = .023). Multiple patterns of FIT kit return were observed: 37% completed FIT at all three time points (full adherence), 22% completed two of three (partial adherence), 29% completed one of three (partial adherence), and 12% did not return any FIT kits (complete nonadherence). Predictors of full adherence were higher levels of education and self‐efficacy.

Conclusions

Full adherence to repeat screening was suboptimal. Most participants had partial adherence (one or two of three) to annual FIT screening. Future studies should focus on strategies to support repeat FIT screening.
Current sharing and voltage restoration based on determination of transmission line resistance considering constant power loads in direct current microgrids
Authors: Mahdavi Milad , Banejad Mahdi , Gholizadeh Narm Hossein , Aminzadeh Hamed
Published: December 2023

Maintaining proper current sharing among distributed generation (DG) units while regulating the output voltage is a challenging control issue in DC microgrids. The conventional droop control is widely used at the primary level of control to tackle this issue, but this method faces some limitations in voltage control and current sharing. To address this problem, this paper presents a new distributed secondary control method that determines the resistance of transmission lines by injecting an external pulse to the reference voltage of each converter and measuring output voltage and current changes. The proposed secondary control signal, denoted as
, enables simultaneous proportional current sharing and voltage restoration in the DC microgrid by correcting the droop coefficients based on the determined resistances. In order to ensure the stability of the proposed method, the small signal stability analysis of the closed‐loop system is conducted, considering various parameter changes. In contrast to similar methods, the proposed method introduces a new hybrid technique of voltage setpoint shifting and droop parameter adjustment that achieves precise proportional current sharing and voltage restoration, even when faced with varying resistive loads and constant power loads (CPLs). Additionally, the proposed method demonstrates outstanding characteristics, such as high convergence speed, the ability to determine transmission line resistances instead of assuming them to be known, and robustness in plug‐and‐play scenarios and communication system failures. The simulation results in MATLAB and experimental tests confirm the effectiveness of the proposed method.
A Gallium Nitride (GaN) Doherty power amplifier chip design based on series RC stability network
Authors: Li Chang‐Kun , Zhu Xiao‐Wei , Liu Rui‐Jia , Zhang Lei
Published: December 2023

This paper presents Doherty power amplifier (DPA) based on gallium nitride (GaN) technology, incorporating a parallel grounded network with series RC elements in front of the carrier and peaking amplifiers to enhance circuit stability. In comparison to the traditional series network with parallel RC structure, this configuration effectively reduces the sensitivity of the stability factorKto the capacitance value within the stability network. Consequently, it mitigates the impact on various performance indicators such as gain and drain efficiency, addressing the issue of measurement performance deviation caused by inaccurate capacitance models in the simulation files, which is particularly crucial for DPA. As a result, the circuit exhibits improved consistency in design and processing. With full band stability, the DPA achieves a saturation output power of approximately 29.8 dBm at 28 GHz, a saturation efficiency of 38.2%, and a 6‐dB back‐off efficiency of 29.6%.
Data‐driven Bayesian network learning analysis on the regulatory mechanism between carcinogenic genes and immune cells
Authors: Bu Weixiao , Mu Huaxia , Gao Mengyao , Su Weiqiang , Shi Fuyan , Wang Qinghua , Wang Suzhen , Kong Yujia
Published: December 2023

Background

In recent years, it has become a research focus to accurately extract key genes influencing the occurrence and development of diseases from massive genomic data and study their regulatory mechanisms. Further exploration of these large databases is beneficial for us to identify key regulatory mechanisms in the occurrence and development of diseases, providing direction and theoretical basis for subsequent experimental design and research.

Methods

By using data from The Cancer Genome Atlas (TCGA) for lung adenocarcinoma (LUAD), the immune cell content of patients was obtained through deconvolution calculations in CIBERSORTx. Combined with Bayesian network inference methods, the impact of key gene expression on the heterocellular network influencing lung cancer was analyzed.

Results

We found CD36 and ADRA1A genes were identified as two key mRNA genes influencing lung adenocarcinoma. The sensitivity analysis shows that the model performs well on both the testing set (error rate = 4%, AUC = 0.9804), the training set (error rate = 5.637%, AUC = 0.9746) and the verification set (error rate = 28.85%, AUC = 0.8689). The model has excellent predictive capabilities.

Conclusion

We found that CD36 and ADRA1A genes may influence the development of lung cancer by affecting regulatory T cell and follicular helper T cell populations. Additionally, plasma cells may affect the expression of the CD36 gene. And the mutual information calculated by the model for these two genes is also the highest, indicating their potential as tumour biomarkers. Combining the network model, it can be inferred that CD36 and ADRA1A are likely to influence the occurrence and development of the disease through follicular helper T cells and regulatory T cells.
The molecular classification of cancer‐associated fibroblasts on a pan‐cancer single‐cell transcriptional atlas
Authors: Chen Bonan , Chan Wai Nok , Xie Fuda , Mui Chun Wai , Liu Xiaoli , Cheung Alvin H. K. , Lung Raymond W. M. , Chow Chit , Zhang Zhenhua , Fang Canbin , Yu Peiyao , Shi Shihua , Zhou Shikun , Chen Guoming , Wang Zhangding , Wang Shouyu , Ding Xiaofan , Huang Bing , Liang Li , Dong Yujuan , Wong Chi Chun , Wu William K. K. , Cheng Alfred S. L. , Wong Nathalie , Yu Jun , Lo Kwok Wai , Tse Gary M. K. , Kang Wei , To Ka Fai
Published: December 2023

Background

Cancer‐associated fibroblasts (CAFs), integral to the tumour microenvironment, are pivotal in cancer progression, exhibiting either pro‐tumourigenic or anti‐tumourigenic functions. Their inherent phenotypic and functional diversity allows for the subdivision of CAFs into various subpopulations. While several classification systems have been suggested for different cancer types, a unified molecular classification of CAFs on a single‐cell pan‐cancer scale has yet to be established.

Methods

We employed a comprehensive single‐cell transcriptomic atlas encompassing 12 solid tumour types. Our objective was to establish a novel molecular classification and to elucidate the evolutionary trajectories of CAFs. We investigated the functional profiles of each CAF subtype using Single‐Cell Regulatory Network Inference and Clustering and single‐cell gene set enrichment analysis. The clinical relevance of these subtypes was assessed through survival curve analysis. Concurrently, we employed multiplex immunofluorescence staining on tumour tissues to determine the dynamic changes of CAF subtypes across different tumour stages. Additionally, we identified the small molecule procyanidin C1 (PCC1) as a target for matrix‐producing CAF (matCAF) using molecular docking techniques and further validated these findings through in vitro and in vivo experiments.

Results

In our investigation of solid tumours, we identified four molecular clusters of CAFs: progenitor CAF (proCAF), inflammatory CAF (iCAF), myofibroblastic CAF (myCAF) and matCAF, each characterised by distinct molecular traits. This classification was consistently applicable across all nine studied solid tumour types. These CAF subtypes displayed unique evolutionary pathways, functional roles and clinical relevance in various solid tumours. Notably, the matCAF subtype was associated with poorer prognoses in several cancer types. The targeting of matCAF using the identified small molecule, PCC1, demonstrated promising antitumour activity.

Conclusions

Collectively, the various subtypes of CAFs, particularly matCAF, are crucial in the initiation and progression of cancer. Focusing therapeutic strategies on targeting matCAF in solid tumours holds significant potential for cancer treatment.
Gender dimorphism in hepatocarcinogenesis—DNA methylation modification regulated X‐chromosome inactivation escape molecule XIST
Authors: Dai Zhihui , Wang Sijie , Guo Xinggang , Wang Yuefan , Yin Haozan , Tan Jian , Mu Chenyang , Sun Shu‐Han , Liu Hui , Yang Fu
Published: December 2023

Background

Sex disparities constitute a significant issue in hepatocellular carcinoma (HCC). However, the mechanism of gender dimorphism in HCC is still not completely understood.

Methods

5‐Hydroxymethylcytosine (5hmC)‐Seal technology was utilised to detect the global 5hmC levels from four female and four male HCC samples. Methylation of XIST was detected by Sequenom MassARRAY methylation profiling between HCC tissues (T) and adjacent normal liver tissues (L). The role of Tet methylcytosine dioxygenase 2 (TET2) was investigated using diethylnitrosamine (DEN)‐administered Tet2−/− female mice, which regulated XIST in hepatocarcinogenesis. All statistical analyses were carried out by GraphPad Prism 9.0 and SPSS version 19.0 software.

Results

The results demonstrated that the numbers of 5hmC reads in the first exon of XIST from female HCC tissues (T) were remarkably lower than that in female adjacent normal liver tissues (L). Correspondingly, DNA methylation level of XIST first exon region was significantly increased in female T than in L. By contrast, no significant change was observed in male HCC patients. Compared to L, the expression of XIST in T was also significantly downregulated. Female patients with higher XIST in HCC had a higher overall survival (OS) and more extended recurrence‐free survival (RFS). Moreover, TET2 can interact with YY1 binding to the promoter region of XIST and maintain the hypomethylation state of XIST. In addition, DEN‐administered Tet2−/− mice developed more tumours than controls in female mice.

Conclusions

Our study provided that YY1 and TET2 could interact to form protein complexes binding to the promoter region of XIST, regulating the methylation level of XIST and then affecting the expression of XIST. This research will provide a new clue for studying sex disparities in hepatocarcinogenesis.

Highlights

XIST was significantly downregulated in HCC tissues and had gender disparity.

Methylation levels in the XIST first exon were higher in female HCC tissues, but no significant change in male HCC patients.

The TET2–YY1 complex regulate XIST expression in female hepatocytes.

Other ways regulate XIST expression in male hepatocytes.
Using community science to map western monarch butterflies (Danaus plexippus) in spring
Authors: Erickson Emily , Jason Christopher , Machiorlete Hannah , de la Espriella Lilianne , Crone Elizabeth E. , Schultz Cheryl B.
Published: December 2023

Migratory animals follow seasonal cycles comprising linked phases often with different habitat requirements and demographic processes. Conservation of migratory species therefore must consider the full seasonal cycle to identify points limiting population viability. For western monarch butterflies, which have experienced significant declines, early spring is considered a critical period in the annual population cycle. However, records of western monarchs in early spring, when overall abundance is lowest, have historically been extremely limited. We used a community science initiative, the Western Monarch Mystery Challenge, to collect data on monarch distribution throughout the western United States between February 14th and April 22nd over 3 years. Using data from the Western Monarch Mystery Challenge and iNaturalist, we identified potential breeding habitat for western monarchs in early spring that spanned a large geographic area and several ecoregions. We observed monarchs in early spring that likely eclosed in the current year, suggesting that population expansion from overwintering sites reflects both movement and population growth. The number of records of western monarchs from early spring was higher during the Mystery Challenge (33.0/year) than earlier years (5.1/year). This study demonstrates the potential for and limitations of community science to increase our understanding of species at points in the life cycle when they are rare.
Resource allocation in 5G cloud‐RAN using deep reinforcement learning algorithms: A review
Authors: Khani Mohsen , Jamali Shahram , Sohrabi Mohammad Karim , Sadr Mohammad Mohsen , Ghaffari Ali
Published: December 2023

This paper reviews recent research on resource allocation in 5G cloud‐based radio access networks (C‐RAN) using deep reinforcement learning (DRL) algorithms. It explores the potential of DRL for learning complex decision‐making policies without human intervention. The paper first introduces the C‐RAN architecture and resource allocation concepts, followed by an overview of DRL algorithms applied to C‐RAN. It discusses the challenges and potential solutions in applying DRL to C‐RAN resource allocation, including scalability, convergence, and fairness. The review concludes by highlighting open research directions for future investigation. By providing insights into the state‐of‐the‐art techniques for resource allocation in 5G C‐RAN using DRL, this paper emphasizes their potential impact on advancing 5G network technology.
A review on mechanisms and impacts of cold plasma treatment as a non‐thermal technology on food pigments
Authors: Ramezan Yousef , Kamkari Amir , Lashkari Armita , Moradi Donya , Tabrizi Abbas Najafi
Published: December 2023

Food characteristics like appearance and color, which are delicate parameters during food processing, are important determinants of product acceptance because of the growing trend toward more diverse and healthier diets worldwide, as well as the increase in population and its effects on food consumption. Cold plasma (CP), as a novel technology, has marked a new trend in agriculture and food processing due to the various advantages of meeting both the physicochemical and nutritional characteristics of food products with minimal changes in physical, chemical, nutritional, and sensorial properties. CP processing has a positive impact on food quality, including the preservation of natural food pigments. This article describes the influence of CP on natural food pigments and color changes in vegetables and fruits. Attributes of natural pigments, such as carotenoids, chlorophyll, anthocyanin, betalain, and myoglobin, are presented. In addition, the characteristics and mechanisms of CP processes were studied, and the effect of CP on mentioned pigments was investigated in recent literature, showing that the use of CP technology led to better preservation of pigments, improving their preservation and extraction yield. While certain modest and undesirable changes in color are documented, overall, the exposure of most food items to CP resulted in minor loss and even beneficial influence on color. More study is needed since not all elements of CP treatment are currently understood. The negative and positive effects of CP on natural food pigments in various products are discussed in this review.
Effects of blending ratio variation on macronutrient compositions and sensory acceptability of dabi teff‐field pea‐based novel composite complementary flours
Authors: Tura Diriba Chewaka , Belachew Tefera , Tamiru Dessalegn , Abate Kalkidan Hassen
Published: December 2023

The response of a mixed system is determined by the proportions of the various ingredients that add up to one, not by the combination's total amount. This research aimed at examining the effects of blending ratio variation on the macro‐composition and sensory acceptability of dabi teff‐field pea‐based novel composite complementary flours. Standard methods (AOAC, 2016, Official Methods of Analysis of the Association of Official Analytical Chemists) were used to determine macronutrients. The sensory attributes were evaluated using a 5‐point hedonic scale. The ingredients were constrained at 0%–30% for field pea, 20%–35% for dabi teff, and 5%–20% for maize, while the remaining were set constant at 5% linseed, 15% oats, and 25% barley. D‐optimal was used to examine the effects of blending ratio variation on the responses. All the responses were significantly different (p < .05) among the blends except for fat content, ranging from 14.58% to 17.21% for protein, 4.22% to 5.59% fat, 2.01% to 2.60% ash, 2.68% to 3.96% fiber, 68.08% to 70.76% utilizable carbohydrate, and 378.82 to 386.9 kcal/100 g gross energy. The sensory acceptability score ranged from 3.4 to 4.4. The linear model was significant (p < .05) and adequate to describe variation in moisture, protein, and ash contents. An increase in the ratio of field pea significantly increased (p < .05) protein, ash, fiber, and energy. The interactive effect between dabi teff and field pea significantly increased the sensory acceptability of the blends. These findings showed that varied proportions of the ingredients had a significant effect on the responses, and were used to develop a wholesome product to combat protein‐energy malnutrition among children.
Effects of non‐condensable CCUS impurities (CH4, O2, Ar and N2) on the saturation properties (bubble points) of CO2‐rich binary systems at low temperatures (228.15–273.15 K)
Authors: Okoro Franklin , Chapoy Antonin , Ahmadi Pezhman , Burgass Rod
Published: December 2023

The present work investigated the effects of some non‐condensable impurities (i.e., N2, O2, CH4, and Ar) on the phase behaviour of CO2‐rich systems at low temperature conditions (228.15–273.15 K). The study focused on bubble point measurements of CO2‐rich systems using the isothermal (pressure–volume) method at different mole fractions of CO2 (99.5%–95%). The obtained experimental data were used to validate multi‐fluid Helmholtz energy approximation (MFHEA) and Peng–Robinson (PR) equations of state (EoSs). For all data points, the measurements’ uncertainties for temperature and pressure were 0.14 K and 0.03 MPa, respectively. While the composition uncertainty of the CO2 systems was a maximum of 0.024%. The findings reveal that as the mole fractions of the impurities increased, the bubble point pressures of the binary mixtures were elevated. Among all the investigated impurities, N2 has the most significant effect on the bubble point pressures of CO2 binary mixture at all the isotherms and compositions. Both MFHEA and PR models agreed well with the measured equilibrium points. For all systems, the average absolute deviations of the measured experimental data against the MFHEA and PR EoSs, were found to be less than 3.4% and 2.2%, respectively. Although the MFHEA EoS overpredicted most of the data points, the overall trend agreed with the experimental data and was consistent with the data available in the literature. The findings imply that the presence of these non‐condensable impurities (even as low as 0.5% mole fraction) increases the risk of two‐phase flow at higher pressures in a CO2‐rich system. © 2023 The Authors. Greenhouse Gases: Science and Technology published by Society of Chemical Industry and John Wiley & Sons Ltd.
Social fund and infant mortality: Evidence from an anti‐poverty policy in Northeast Brazil
Authors: de Souza Sá Álvaro Robério , Santos Branco Danyelle Karine
Published: December 2023

This paper evaluates the effects of a social fund that meets the needs of the poor in Northeast Brazil, the Fundos Estaduais de Combate e Erradicação da Pobreza (FECEP). The program could have improved infant health by reducing poverty and improving access to health care, sanitation, food, and housing. Using a difference‐in‐differences approach robust to heterogeneous treatment effects, we confirm that the program has effectively reduced poverty in treated areas. Furthermore, we document that this poverty reduction is associated with a significant decline in infant mortality. These findings provide consistent evidence that targeted public investments can improve living conditions in vulnerable regions.
Mechanism of non‐small cell lung cancer cell‐derived exosome miR‐196b‐5p promoting pyroptosis of tumor T cells and tumor cell proliferation by downregulating ING5
Authors: Zhang Zhixian , Yang Lei , Lei Xuefen , Yu Jia , Wang Lijuan , Cao Hongming , Gu Hou
Published: December 2023

In the world, lung cancer is one of the most common malignant cancers and has become the leading cause of death of cancers in China, among which non‐small cell lung cancer (NSCLC) accounts for a relatively high proportion, but there is a lack of effective treatment at present. An animal model of NSCLC was established, and BEAS‐2b, H1299, Lewis, and T cells were used for subsequent experimental verification. The level of miR‐196b‐5p was detected by quantitative real‐time polymerase chain reaction. Growth inhibitor 5 (ING5), CD9, CD63, HSP70, Caspase‐1, NLRP3, and GSDMD‐NT were detected by western blot. The level of ING5 was confirmed by immunohistochemistry, the location of miR‐196b‐5p was analyzed by fluorescence in situ hybridization (FISH), cell viability was investigated by Cell Counting Kit‐8 kit, and interleukin (IL)‐1β and IL‐18 were confirmed by enzyme‐linked immunosorbent assay. Cell apoptosis was detected by flow cytometry. In addition, the binding site was verified by dual‐luciferase reporter gene experiments. Tumor volume was measured. TUNEL staining was used to detect apoptosis. Flow cytometry was used to measure the levels of CD8 T, CD4 T, and Treg cells in tumors. miR‐196‐5p was highly expressed in exosomes secreted by tumor cells. miR‐196‐5p negatively targeted ING5 to promote the growth of tumor cells. Cancer‐derived exosomes promote pyroptosis of T cells to further aggravate the development of cancer. Exosome‐derived miR‐196b‐5p promoted pyroptosis of T cells. Exosome‐derived miR‐196b‐5p inhibited the level of ING5 to promote tumor growth and accelerate the process of NSCLC.
DFT insights into LaFeO3 with Mn substitution: A promising path to energy‐efficient magneto‐optical applications
Authors: Tariq Saad , Alrashdi Ayash O , Al Bahir Areej , Gilani S. M. Sohail , Hamioud Farida , Mubarak A. A. , Ahmed Afaq , Saad H.‐E M. Musa
Published: December 2023

In recent years, the demand for electronic materials has significantly increased, driven by industrial needs and the pursuit of cost‐efficient alternatives. This comprehensive study investigates the effects of Mn substitution on LaFeO3 through the implementation of the GGA approach in density functional theory. The research findings demonstrate remarkable consistency with the experimental outcomes reported in the existing literature pertaining to the studied compounds. However, this study unveils novel insights into the mechanical and optical characteristics of the doped structures, which have not been previously reported. The structural stability is rigorously examined through multiple stability criteria, encompassing structural optimization, tests of elastic stability, and enthalpy of formation calculations. Furthermore, the electronic and optical properties of the compounds exhibit exceptional improvements in conductivity and reflectivity as a result of the doping process. The band structure analysis reveals the presence of a Moss‐Burstein shift. Investigation of the magnetic properties indicates an increase in the magnetic moment value due to the Fe‐Mn degeneracy resulting from increased Mn content. Mechanical analysis of the elastic moduli B, G, and Y demonstrates an enhanced strength and metal‐like conductivity, attributed to the induced anharmonicity. Moreover, the internal strain factor suggests a higher degree of bond flexibility, implying potential applications of these compounds in flexible electronics.
miRNA profiling of granulosa cell‐derived exosomes reveals their role in promoting follicle development
Authors: Zhou Qilin , Liu Zhen , Liao Zhengdong , Zhang Yangzhuohan , Qu Mengyuan , Wu Fanggui , Tian Jingyan , Zhao Huan , Peng Qianwen , Zheng Wenchao , Huang Mingyuan , Yang Sheng
Published: December 2023

To explore whether granulosa cell (GC)‐derived exosomes (GC‐Exos) and follicular fluid‐derived exosomes (FF‐Exos) have functional similarities in follicle development and to establish relevant experiments to validate whether GC‐Exos could serve as a potential substitute for follicular fluid‐derived exosomes to improve folliculogenesis. GC‐Exos were characterized. MicroRNA (miRNA) profiles of exosomes from human GCs and follicular fluid were analyzed in depth. The signature was associated with folliculogenesis, such as phosphatidylinositol 3 kinases‐protein kinase B signal pathway, mammalian target of rapamycin signal pathway, mitogen‐activated protein kinase signal pathway, Wnt signal pathway, and cyclic adenosine monophosphate signal pathway. A total of five prominent miRNAs were found to regulate the above five signaling pathways. These miRNAs include miRNA‐486‐5p, miRNA‐10b‐5p, miRNA‐100‐5p, miRNA‐99a‐5p, and miRNA‐21‐5p. The exosomes from GCs and follicular fluid were investigated to explore the effect on folliculogenesis by injecting exosomes into older mice. The proportion of follicles at each stage is counted to help us understand folliculogenesis. Exosomes derived from GCs were isolated successfully. miRNA profiles demonstrated a remarkable overlap between the miRNA profiles of FF‐Exos and GC‐Exos. The shared miRNA signature exhibited a positive influence on follicle development and activation. Furthermore, exosomes derived from GCs and follicular fluid promoted folliculogenesis in older female mice. Exosomes derived from GCs had similar miRNA profiles and follicle‐promoting functions as follicular fluid exosomes. Consequently, GC‐Exos are promising for replacing FF‐Exos and developing new commercial reagents to improve female fertility.