bluuebunny/crossref_metadata_2025 huggingface dataset:
Curcumin relieves oxaliplatin‐induced neuropathic pain via reducing inflammation and activating antioxidant response
Authors: Zhang Meng‐Wei , Sun Xu , Xu Yi‐Wen , Meng Wei , Tang Qiong , Gao Hui , Liu Ling , Chen Shao‐Hui
Published: March 2024

Oxaliplatin (OXA) has shown high effectiveness in the treatment of cancers, but its anticancer clinical effects often induce neurotoxicity leading to neuropathic pain. Oxidative damage and NLRP3 inflammasome play important roles in neuropathic pain development. Here, neuropathic pain mouse model was constructed by continuous intraperitoneal injection of OXA. OXA administration induced mechanical pain, spontaneous pain, thermal hyperalgesia and motor disability in mice. The spinal cord tissues of OXA mice exhibited the suppressed antioxidative response, the activated NLRP3 inflammasome mediated inflammatory responses, and the increased GSK‐3β activity. Next, we injected curcumin (CUR) intraperitoneally in OXA mice for seven consecutive days. CUR‐treated mice showed increased mechanical pain thresholds, reduced number of spontaneous flinches, increased paw withdrawal latency, and restored latency to fall. While in the spinal cord, CUR treatment inhibited the NLRP3 inflammasome mediated inflammatory response, increased Nrf2/GPX4‐mediated antioxidant responses, and decreased mitochondrial oxidative generation. Additionally, CUR combined with GSK‐3β through four covalent bonds and reduced GSK‐3β activity. In conclusion, our findings suggest that CUR treatment inhibits GSK‐3β activation, increases Nrf2 mediated antioxidant responses, inhibits oxidative damage and inflammatory reaction, and alleviates OXA‐induced neuropathic pain.
Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta‐analysis
Authors: Sagris Marios , Ktenopoulos Nikolaos , Dimitriadis Kyriakos , Papanikolaou Angelos , Tzoumas Andreas , Terentes‐Printzios Dimitrios , Synetos Andreas , Soulaidopoulos Stergios , Lichtenberg Michael , Korosoglou Grigorios , Honton Benjamin , Tousoulis Dimitris , Tsioufis Costas , Toutouzas Konstantinos
Published: March 2024

Background

With heavily calcified coronary and peripheral artery lesions, lesion preparation is crucial before stent placement to avoid underexpansion, associated with stent thrombosis or restenosis and patency failure in the long‐term. Intravascular lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, making it to a promising tool for patients with severe calcification in coronary bed.

Aims

The aim of the study is to systematically review and summarize available data regarding the safety and efficacy of IVL for lesion preparation in severely calcified coronary arteries before stenting.

Methods

This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL, as well as stent implantation, were analyzed. The occurrence of major adverse cardiovascular events (MACE) was assessed using a random‐effects model.

Results

This meta‐analysis comprised 38 studies including 2977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL clinical success of 93% (95% confidence interval [CI]: 91%−95%,I2 = 0%) and procedural success rate of 97% (95% CI: 95%−98%,I2 = 73.7%), while the in‐hospital and 30‐days incidence of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%−11%,I2 = 84.5%), 5% (95% CI: 2%−8%,I2 = 85.6%), and 2% (95% CI: 1%−3%,I2 = 69.3%), respectively. There was a significant increase in the vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77−3.17,I2 = 96%) and a decrease in diameter stenosis (SMD: −3.44, 95% CI: −4.36 to −2.52,I2 = 97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: −6.57, 95% CI: −7.43 to −5.72,I2 = 95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63−5.12,I2 = 96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10−4.37,I2 = 98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6 and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with just a few cases of perforations, dissection, or no‐reflow phenomena recorded.

Conclusions

IVL seems to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.
Elderly onset of MELAS carried an M.3243A >G mutation in a female with deafness and visual deficits: A case report
Authors: Zijun Lin , Xu Yi , Yujia Yang , Zhiqiang Xu
Published: March 2024

Key Clinical Message

MELAS is a disorder with clinical variability that also responsible for a significant portion of unexplained hereditary or childhood‐onset hearing loss. Although patients typically present in childhood, the first stroke‐like episode can occur later in life in some patients, potentially related to a lower heteroplasmy level. It is crucial to consider MELAS as a potential cause of stroke‐like events if age at presentation and symptoms are atypical, especially among middle‐aged patients without vascular risk factors.

MELAS syndrome (mitochondrial encephalopathy with lactic acidosis and stroke‐like episodes) is a rare genetic condition that most patients develop stroke‐like episodes before the age of 40. We report a 52‐year‐old female with a documented 40‐year history of progressive sensorineural hearing loss, developed a visual field deficit and stroke‐like events in her middle age who finally diagnosed was MELAS. The patient was started on vitamin E, l‐carnitine, l‐arginine, and coenzyme Q10 that gradually improved before dismissal from the hospital. This case highlights the importance of considering MELAS as a potential cause of stroke‐like events if imaging findings are atypical for cerebral infarction, especially among middle‐aged patients without vascular risk factors and an unusual cause of progressive sensorineural hearing loss.
Fiberoptic endoscopic assessment of dysphagia in a patient with cutaneous and oropharyngeal blisters
Authors: Bartholow Allison Hughes
Published: March 2024

Key Clinical Message

Dysphagia resulting from bulbous pemphigoid is a rare but significant manifestation. A 77‐year‐old with bullous pemphigoid with no neurological history presented with severe oropharyngeal dysphagia, attributable to underlying blistering and edema, as documented on a fiberoptic endoscopic swallow examination.
Building stabilized Cu0.17Mn0.03V2O5−□·2.16H2O cathode enables an outstanding room‐/low‐temperature aqueous Zn‐ion batteries
Authors: Wang Ao , Liu Dai‐Huo , Yang Lin , Xu Fang , Luo Dan , Dou Haozhen , Song Mengqin , Xu Chunyan , Zhang Beinuo , Zheng Jialin , Chen Zhongwei , Bai Zhengyu
Published: March 2024

Vanadium oxide cathode materials with stable crystal structure and fast Zn2+ storage capabilities are extremely important to achieving outstanding electrochemical performance in aqueous zinc‐ion batteries. In this work, a one‐step hydrothermal method was used to manipulate the bimetallic ion intercalation into the interlayer of vanadium oxide. The pre‐intercalated Cu ions act as pillars to pin the vanadium oxide (V‐O) layers, establishing stabilized two‐dimensional channels for fast Zn2+ diffusion. The occupation of Mn ions between V‐O interlayer further expands the layer spacing and increases the concentration of oxygen defects (Od), which boosts the Zn2+ diffusion kinetics. As a result, as‐prepared Cu0.17Mn0.03V2O5−□·2.16H2O cathode shows outstanding Zn‐storage capabilities under room‐ and low‐temperature environments (e.g., 440.3 mAh g−1 at room temperature and 294.3 mAh g−1 at −60°C). Importantly, it shows a long cycling life and high capacity retention of 93.4% over 2500 cycles at 2 A g−1 at −60°C. Furthermore, the reversible intercalation chemistry mechanisms during discharging/charging processes were revealed via operando X‐ray powder diffraction and ex situ Raman characterizations. The strategy of a couple of 3d transition metal doping provides a solution for the development of superior room‐/low‐temperature vanadium‐based cathode materials.
Multicationic Tetrahedra Networks: Alkaline‐Earth‐Centered Polyhedra and Non‐Condensed AlN6‐Octahedra in the Imidonitridophosphates AE2AlP8N15(NH) (AE=Ca, Sr, Ba)
Authors: Pointner Monika M. , Pritzl Reinhard M. , Albrecht Jonas M. , Blahusch Leopold , Wright Jonathan P. , Bright Eleanor Lawrence , Giacobbe Carlotta , Oeckler Oliver , Schnick Wolfgang
Published: March 2024

A series of isostructural imidonitridophosphates AE2AlP8N15(NH) (AE=Ca, Sr, Ba) was synthesized at high‐pressure/high‐temperature conditions (1400 °C and 5–9 GPa) from alkaline‐earth metal nitrides or azides Ca3N2/Sr(N3)2/Ba(N3)2 and the binary nitrides AlN and P3N5. NH4F served as a hydrogen source and mineralizing agent. The crystal structures were determined by single‐crystal X‐ray diffraction and feature a three‐dimensional network of vertex‐sharing PN4‐tetrahedra forming diverse‐sized rings that are occupied by aluminum and alkaline earth ions. These structures represent another example of nitridophosphate‐based networks that simultaneously incorporate AlN6‐octahedra and alkaline‐earth‐centered polyhedra, with aluminum not participating in the tetrahedra network. They differ from previously reported ones by incorporating non‐condensed octahedra instead of strongly condensed octahedra units and contribute to the diversity of multicationic nitridophosphate network structures. The results are supported by atomic resolution EDX mapping, solid‐state NMR and FTIR measurements. Eu2+‐doped samples show strong luminescence with narrow emissions in the range of green to blue under UV excitation, marking another instance of Eu2+‐luminescence within imidonitridophosphates.
Photocatalytic Site‐Selective Cascade Radical Addition of Biaryl Ynones for the Construction of Spiro‐ and Fused Carbon Rings
Authors: Liu Kairui , Zhao Chunhang , Gu Liji , Li Xiang , Yan Jiali , Lao Siqi , Huan Weiwei , Zhang Yan
Published: March 2024

Comprehensive Summary

Functionalized free radical addition/cyclization reactions represent an efficient way for introducing new functionality or coupling fragments to molecules. Ynones are good regional selectivity radical acceptors in organic synthesis, and many of bio‐relevant cyclic compounds could be easily obtained by direct radical cyclization reaction. Here, we report a photocatalytic cascade radical addition of biaryl ynones, for the divergent synthesis of privileged carbon cycles. Additionally, further transformation of the multi‐functional group product into a variety of other derivatives demonstrates the synthetic value of this developed method.
Retino‐dural hemorrhages in infants are markers of degree of intracranial pathology, not of violent shaking
Authors: Brook Chris
Published: March 2024

Aim

This study analyzed whether retino‐dural hemorrhages in infants are markers of the degree of intracranial pathology, rather than evidence of violent shaking.

Methods

Using data from 420 infants with acute intracranial pathologies, comparison of clinical findings is made between cases diagnosed as abusive head trauma (AHT) and four categories: cases where caregivers report no trauma; cases of witnessed or admitted AHT; cases where caregivers report accidental trauma; and witnessed accidents. The data are then controlled for degree of intracranial pathology by only comparing cases in each category that have evidence of hypoxic‐ischemic swelling.

Results

Although categories differ in clinical findings when all data are considered, they do not differ when the data are controlled for degree of intracranial pathology.

Conclusions

The data suggest that the clinical findings widely considered to be indicative of shaking are instead markers of the degree of intracranial pathology. Previous results showing differences were driven by selection effects, whereby different categories have different fractions of serious cases. Most notably, caregiver and witnessed reports of accidental head trauma led doctors to explore intracranial pathologies across a broader spectrum of severity, including milder cases, as opposed to situations where no head trauma is reported.
Gene Polymorphisms of NLRP3 Associated With Plasma Levels of 4β‐Hydroxycholesterol, an Endogenous Marker of CYP3A Activity, in Patients With Asthma
Authors: Hirai Keita , Kimura Tomoki , Suzuki Yuya , Shimoshikiryo Takayuki , Shirai Toshihiro , Itoh Kunihiko
Published: March 2024

Inflammation decreases the activity of cytochrome P450 3A (CYP3A). Nucleotide‐binding oligomerization domain (NOD)‐like receptor family pyrin domain containing 3 (NLRP3) is responsible for regulating the inflammatory response, and its genetic polymorphisms have been linked to inflammatory diseases such as asthma. However, there have been few studies on the effect of NLRP3 on CYP3A activity. We aimed to investigate the association between polymorphisms in the NLRP3 gene and plasma 4β‐hydroxycholesterol (4βOHC), an endogenous marker of CYP3A activity, in patients with asthma. In this observational study including 152 adult asthma patients, we analyzed 10 NLRP3 gene single‐nucleotide polymorphisms (SNPs). Plasma 4βOHC levels were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The results showed that five SNPs were associated with significantly lower plasma 4βOHC concentrations. Among these SNPs, rs3806265, rs4612666, rs1539019, and rs10733112 contributed to a significant increase in plasma IL‐6 concentrations. Moreover, a multivariate regression model showed that the rs3806265 TT, rs4612666 CC, rs1539019 AA, and rs10733112 TT genotypes were significant factors for decreased plasma 4βOHC, even after including patient background factors and CYP3A5*3 (rs776746) gene polymorphisms as covariates. These results were also observed when plasma 4βOHC concentrations were corrected for cholesterol levels. We conclude that NLRP3 gene polymorphisms are involved in increasing plasma IL‐6 concentrations and decreasing plasma 4βOHC concentrations in patients with asthma. Therefore, NLRP3 gene polymorphisms may be a predictive marker of CYP3A activity in inflammatory diseases such as asthma.
Downregulation of salivary miR‐3928 as a potential biomarker in patients with oral squamous cell carcinoma and oral lichen planus
Authors: Farshbaf Alieh , Mohajertehran Farnaz , Aghaee‐Bakhtiari Seyed Hamid , Ayatollahi Hossein , Douzandeh Katayoun , Pakfetrat Atessa , Mohtasham Nooshin
Published: March 2024

Objectives

Recent studies highlighted the role of miR expressed in saliva as reliable diagnostic and prognostic tools in the long‐term monitoring of cancer processes such as oral squamous carcinoma (OSCC). Based on a few previous studies, it seems the miR‐3928 can be considered a master regulator in carcinogenesis, and it can be therapeutically exploited. This is the first study that compared oral potentially malignant disorder (OLP) and malignant (OSCC) lesions for miR‐3928 expression.

Materials and Methods

In this cross‐sectional study, saliva samples from 30 healthy control individuals, 30 patients with erosive/atrophic oral lichen planus, and 31 patients with OSCC were collected. The evaluation of miR‐3928 expression by q‐PCR and its correlation with clinicopathological indices were analyzed by Shapiro−Wilk, Kruskal−Wallis, Pearson's χ2, and Mann−Whitney tests. The p‐value less than .05 indicated statistically significant results.

Results

Based on nonparametric Kruskal−Wallis test results, there was a statistically significant difference between the ages of three study groups (p < .05). This test demonstrated a statistically significant difference between the average of miR‐3928 expression in three study groups (p < .05). The result of the χ2 test showed a statistically significant difference in miR‐3928 expression between patients with OLP (p = .01) and also patients with OSCC (p < .0001) in comparison to the control group.

Conclusions

The salivary miR‐3928 can play a tumor suppressive role in the pathobiology of OSCC, and it is significantly downregulated in patients. According to the potential tumor suppressive role of miR‐3928 in the OSCC process, we can consider this microRNA as a biomarker for future early diagnosis, screening, and potential target therapy.
Effect of Gas Composition on Temperature and CO2 Conversion in a Gliding Arc Plasmatron reactor: Insights for Post‐Plasma Catalysis from Experiments and Computation
Authors: Xu Wencong , Van Alphen Senne , Galvita Vladimir V. , Meynen Vera , Bogaerts Annemie
Published: March 2024

Plasma‐based CO2 conversion has attracted increasing interest. However, to understand the impact of plasma operation on post‐plasma processes, we studied the effect of adding N2, N2/CH4 and N2/CH4/H2O to a CO2 gliding arc plasmatron (GAP) to obtain valuable insights into their impact on exhaust stream composition and temperature, which will serve as feed gas and heat for post‐plasma catalysis (PPC). Adding N2 improves the CO2 conversion from 4 % to 13 %, and CH4 addition further promotes it to 44 %, and even to 61 % at lower gas flow rate (6 L/min), allowing a higher yield of CO and hydrogen for PPC. The addition of H2O, however, reduces the CO2 conversion from 55 % to 22 %, but it also lowers the energy cost, from 5.8 to 3 kJ/L. Regarding the temperature at 4.9 cm post‐plasma, N2 addition increases the temperature, while the CO2/CH4 ratio has no significant effect on temperature. We also calculated the temperature distribution with computational fluid dynamics simulations. The obtained temperature profiles (both experimental and calculated) show a decreasing trend with distance to the exhaust and provide insights in where to position a PPC bed.
Xanthones with multiple roles against diabetes: their synthesis, structure‐activity relationship, and mechanism studies
Authors: Ke Youhong , Xu Qinfang , Hu Jianling , Zhang Jianrun , Chen Shijian , Liu Zhijun , Peng Shuling , Zhang Chao , Chen Zhenqiang , Chen Heru
Published: March 2024

A four‐step synthetic process has been developed to prepare 1,3,5,8‐tetrahydroxyxanthone (2a) and its isomer 1,3,7,8‐tetrahydroxyxanthone (2b). 25 more xanthones were also synthesized by a modified scheme. Xanthone 2a was identified as the most active inhibitor against both α‐glucosidase and aldose reductase (ALR2), with IC50 values of 7.8 ± 0.5 μM and 63.2 ± 0.6 nM, respectively, which was far active than acarbose (35.0 ± 0.1 μM), and a little more active than epalrestat (67.0 ± 3.0 nM). 2a was also confirmed as the most active antioxidant in vitro with EC50 value of 8.9 ± 0.1 μM. Any structural modification including methylation, deletion, and position change of hydroxyl group in 2a will cause an activity loss in inhibitory and antioxidation. By applying a H2O2‐induced oxidative stress nematode model, it was confirmed that xanthone 2a can be absorbed by Caenorhabditis elegans and is bioavailable to attenuate in vivo oxidative stress, including the effects on lifespan, superoxide dismutase, Catalase, and malondialdehyde. 2a was verified with in vivo hypoglycemic effect and mitigation of embryo malformations in high glucose. All our data support that xanthone 2a behaves triple roles and is a potential agent to treat diabetic mellitus, gestational diabetes mellitus, and diabetic complications.
Comprehensive analysis of vitamin D3 impurities in oily drug products using supercritical fluid chromatography–mass spectrometry
Authors: Jambo Hugues , Dispas Amandine , Pérez‐Mayán Leticia , Rodríguez Isaac , Ziemons Éric , Hubert Philippe
Published: March 2024

Vitamin D3, an essential micronutrient, often requires supplementation via medicines or food supplements, which necessitate quality control (QC). This study presents the development of a method for detecting and quantifying seven impurities of vitamin D3 in oily drug products using supercritical fluid chromatography–mass spectrometry (SFC‐MS). Targeted impurities include two esters of vitamin D3 and five non‐esters including four that are isobaric to vitamin D3. Firstly, a screening study highlighted the Torus 1‐AA column and acetonitrile modifier as adequate for the separation, followed by optimization of the SFC conditions. Secondly, make‐up solvent composition and MS settings were optimized to reach high sensitivity. For both the separation and MS response, the screening design of experiments proved useful. Lastly, a fast saponification and liquid–liquid extraction method was developed, enabling efficient sample cleanup and impurities recovery from the complex oily matrix. The SFC‐MS method suitability was assessed in two validation studies. The first study employed the ICH Q2 guideline for impurity limit test to demonstrate method specificity and establish a limit of detection (LOD) and a limit of quantification (LOQ) at 0.2% and 0.5%, respectively, for ester impurities. The second study conducted a comprehensive quantitative assessment for three non‐ester impurities using a total error approach, determining method validity through accuracy profiles. The validated method exhibited reliable performance across impurity concentrations from 0.1% to 2.0%, with estimated LODs ranging from 2 to 7 ng/mL. This study further promotes SFC‐MS as a valuable, versatile, and green tool for routine pharmaceutical QC.
Elucidating the Structure of the Eu‐EDTA Complex in Solution at Various Protonation States
Authors: Licup Gerra L. , Summers Thomas J. , Sobrinho Josiane A. , de Bettencourt‐Dias Ana , Cantu David C.
Published: March 2024

Ethylenediaminetetraacetic acid (EDTA), which has two amine and four carboxylate protonation sites, forms stable complexes with lanthanide ions. This work analyzes the coordination structure, in atomic resolution, of the Eu3+ ion complexed with EDTA in all its protonation states in aqueous solution. Eu‐EDTA complexes were modeled using classical molecular dynamics (MD) simulations using force field parameters optimized with ab initio molecular dynamics (AIMD) simulations. Structures from the MD simulations were used to predict extended X‐ray absorption fine structure (EXAFS) spectra and compared with EXAFS measurements of the Eu3+ aqua ion and Eu‐EDTA complexes at pH 3 and 11. This work details how Eu‐EDTA complex coordination structures change with increasing protonation of the EDTA ligand in the complex, from the tightly bound unprotonated complex to the unbinding of the fully protonated EDTA ligand from the Eu3+ ion as both become solvated by water. Agreement between predicted and measured EXAFS spectra supports the findings from simulation.
The usefulness of NDDI‐E and QOLIE‐10 scales for the screening of major depressive disorders in patients with epilepsy in video‐EEG units
Authors: Mayo Rodríguez Pablo , Parejo‐Carbonell Beatriz , Sanz Graciani Isabel , Romeral Jiménez María , De la Cruz Moreno María Cristina , Lastras Clara , Sánchez‐del‐Hoyo Rafael , García Morales Irene
Published: March 2024

Objective

Mood disorders in patients with epilepsy are common, with depression being the most prevalent. However, this comorbidity is often underdiagnosed. The systematic use of scales such as NDDI‐E and QOLIE‐10 in prolonged video‐EEG monitoring units could be a useful tool for the detection of this comorbidity.

Methods

Descriptive cross‐sectional study of a series of patients with epilepsy evaluated in a prolonged video‐EEG monitoring unit.

Results

Three hundred forty‐nine patients were included. The mean age was 49.1 years, and 49.3% were female. 66.2% had focal epilepsy. 20.4% had pharmacoresistant epilepsy. 38.7% of patients had NDDI‐E > 13. 43% of patients with focal epilepsy had NDDI‐E > 13 versus 21.8% of patients with idiopathic generalized epilepsy (p = .015). Patients with focal temporal epilepsy had the highest rate of NDDI‐E > 13 (48.5%). Significant association was found between patient‐perceived mood and NDDI‐E score (p < .001). However, in the group of patients with NDDI‐E > 13, 37.6% had reported feeling “very good” or “good” in mood. Likewise, in the group that had reported feeling “very good” or “good” 21.6% had NDDI‐E > 13. In 50.5% of patients with NDDI‐E > 13 some kind of therapeutic intervention aimed at this comorbidity was performed. Perceived quality of life as measured by the QOLIE‐10 scale was lower in patients with NDDI‐E > 13 (p < .001).

Significance

The use of scales such as the NDDI‐E and QOLIE‐10 at the time of admission in video‐EEG monitoring units allows screening for major depressive disorders in patients with epilepsy, which subsequently needs to be confirmed by formal assessment by a psychiatrist. Their systematic use in these units prevents some patients from going undiagnosed. Detection of these disorders allows targeted therapeutic intervention.
EWA‐DA‐based resource allocation method for 5G networks
Authors: Teja Panduranga Ravi , Mishra Pavan Kumar , Gupta Dharmendra Lal
Published: March 2024

In 5G networks, most D2D work focuses on optimizing system throughput without addressing economic constraints. This article encourages users to exchange resources and apply honest bidding tactics to attain high auction efficiency. This study describes an experience‐weighted attraction double auction (EWA‐DA) technique for allocating resources in 5G D2D networks. The suggested method classifies mobile users into seller cellular users (SCU) and buyer cellular users' (BCU). The SCU transmits the beacon packet, and the nearby cellular users create a D2D group in response to the beacon considered BCU. Then, the bid values of the buyer and seller cellular users are transmitted to the base station side. The BS uses an experience‐weighted attraction‐learning model to obtain accurate bidding prices. Lastly, an ask‐to‐mean‐value double auction model was utilized instead of accurate bid values. Extensive simulation results demonstrate that the suggested strategy delivers excellent auction efficiency and fair earnings for both seller and buyer users. In addition, we identified that the participating users accomplished truthful bidding and used fewer resource blocks than existing techniques.
Skogea, a replacement name for Actinostephanus F. Wen, Y. G. Wei, and L. F. Fu (Gesneriaceae: Didymocarpoidae)
Authors: Deshmukh Umakant B.
Published: March 2024

A replacement generic name, Skogea U. B. Deshmukh, is proposed for the name of the recently described genus Actinostephanus F. Wen, Y. G. Wei, and L. F. Fu (Gesneriaceae: Didymocarpoidae) segregated from Boeica C.B. Clarke, Rhynchotechum Blume, and Leptoboea Benth. because the name Actinostephanus has been recommended to be treated as a later homonym of Actinostephanos Khursevich (Bacillariophyta) by the nomenclature committee for algae.
Upregulation of the secretory pathway Ca2+/Mn2+‐ATPase isoform 1 in LPS‐stimulated microglia and its involvement in Mn2+‐induced Golgi fragmentation
Authors: Bhojwani‐Cabrera Aysha M. , Bautista‐García Alicia , Neubrand Veronika E. , Membrive‐Jiménez Francisco A. , Bramini Mattia , Martin‐Oliva David , Cuadros Miguel A. , Marín‐Teva José Luis , Navascués Julio , Vangheluwe Peter , Sepúlveda M. Rosario
Published: March 2024

Microglia play an important protective role in the healthy nervous tissue, being able to react to a variety of stimuli that induce different intracellular cascades for specific tasks. Ca2+ signaling can modulate these pathways, and we recently reported that microglial functions depend on the endoplasmic reticulum as a Ca2+ store, which involves the Ca2+ transporter SERCA2b. Here, we investigated whether microglial functions may also rely on the Golgi, another intracellular Ca2+ store that depends on the secretory pathway Ca2+/Mn2+‐transport ATPase isoform 1 (SPCA1). We found upregulation of SPCA1 upon lipopolysaccharide stimulation of microglia BV2 cells and primary microglia, where alterations of the Golgi ribbon were also observed. Silencing and overexpression experiments revealed that SPCA1 affects cell morphology, Golgi apparatus integrity, and phagocytic functions. Since SPCA1 is also an efficient Mn2+ transporter and considering that Mn2+ excess causes manganism in the brain, we addressed the role of microglial SPCA1 in Mn2+ toxicity. Our results revealed a clear effect of Mn2+ excess on the viability and morphology of microglia. Subcellular analysis showed Golgi fragmentation and subsequent alteration of SPCA1 distribution from early stages of toxicity. Removal of Mn2+ by washing improved the culture viability, although it did not effectively reverse Golgi fragmentation. Interestingly, pretreatment with curcumin maintained microglia cultures viable, prevented Mn2+‐induced Golgi fragmentation, and preserved SPCA Ca2+‐dependent activity, suggesting curcumin as a potential protective agent against Mn2+‐induced Golgi alterations in microglia.
Integrated transcriptome and proteome analyses reveal potential mechanisms in Stipa breviflora underlying adaptation to grazing
Authors: Liu Yanan , Sun Shixian , Zhang Yanan , Song Miaomiao , Tian Yunyun , Lockhart Peter J. , Zhang Xin , Xu Ying , Dang Zhenhua
Published: March 2024

Background

Long‐term overgrazing has led to severe degradation of grasslands, posing a significant threat to the sustainable use of grassland resources.

Methods

Based on the investigation of changes in functional traits and photosynthetic physiology of Stipa breviflora under no grazing, moderate grazing, and heavy grazing treatments, the changes in expression patterns of genes and proteins associated with different grazing intensities were assessed through integrative transcriptomic and proteomic analyses.

Results

Differentially expressed genes and proteins were identified under different grazing intensities. They were mainly related to RNA processing, carbon metabolism, and secondary metabolite biosynthesis. These findings suggest that long‐term grazing leads to molecular phenotypic plasticity, affecting various biological processes and metabolic pathways in S. breviflora. Correlation analysis revealed low correlation between the transcriptome and the proteome, indicating a large‐scale regulation of gene expression at the posttranscriptional and translational levels during the response of S. breviflora to grazing. The expression profiles of key genes and proteins involved in photosynthesis and phenylpropanoid metabolism pathways suggested their synergistic response to grazing in S. breviflora.

Conclusions

Our study provides insight into the adaptation mechanisms of S. breviflora to grazing and provides a scientific basis for the development of more efficient grassland protection and utilization practices.
Concomitant inhibition of the thioredoxin system and nonhomologous DNA repair potently sensitizes Philadelphia‐positive lymphoid leukemia to tyrosine kinase inhibitors
Authors: Komorowski Lukasz , Dabkowska Agnieszka , Madzio Joanna , Pastorczak Agata , Szczygiel Kacper , Janowska Martyna , Fidyt Klaudyna , Bielecki Maksymilian , Hunia Jaromir , Bajor Malgorzata , Stoklosa Tomasz , Winiarska Magdalena , Patkowska Elzbieta , Firczuk Malgorzata
Published: March 2024

Breakpoint cluster region‐Abelson (BCR::ABL1) gene fusion is an essential oncogene in both chronic myeloid leukemia (CML) and Philadelphia‐positive (Ph+) B‐cell acute lymphoblastic leukemia (B‐ALL). While tyrosine kinase inhibitors (TKIs) are effective in up to 95% of CML patients, 50% of Ph+ B‐ALL cases do not respond to treatment or relapse. This calls for new therapeutic approaches for Ph+ B‐ALL. Previous studies have shown that inhibitors of the thioredoxin (TXN) system exert antileukemic activity against B‐ALL cells, particularly in combination with other drugs. Here, we present that peroxiredoxin‐1 (PRDX1), one of the enzymes of the TXN system, is upregulated in Ph+ lymphoid as compared to Ph+ myeloid cells. PRDX1 knockout negatively affects the viability of Ph+ B‐ALL cells and sensitizes them to TKIs. Analysis of global gene expression changes in imatinib‐treated, PRDX1‐deficient cells revealed that the nonhomologous end‐joining (NHEJ) DNA repair is a novel vulnerability of Ph+ B‐ALL cells. Accordingly, PRDX1‐deficient Ph+ B‐ALL cells were susceptible to NHEJ inhibitors. Finally, we demonstrated the potent efficacy of a novel combination of TKIs, TXN inhibitors, and NHEJ inhibitors against Ph+ B‐ALL cell lines and primary cells, which can be further investigated as a potential therapeutic approach for the treatment of Ph+ B‐ALL.
Anti‐inflammatory potential of remimazolam: A laboratory and clinical investigation
Authors: Tsukimoto Shota , Kitaura Atsuhiro , Kuroda Hidetaka , Imaizumi Uno , Yoshino Fumihiko , Yoshida Ayaka , Nakao Shinchi , Ohta Noriyuki , Nakajima Yasuhumi , Sanuki Takuro
Published: March 2024

Background

Anesthetic agents, particularly intravenous anesthetics, may affect immune function and tumorigenic factors. We herein investigated whether the anti‐inflammatory effects of anesthetic agents are attributed to their antioxidant properties. The antioxidant and anti‐inflammatory effects of remimazolam, a new anesthetic, remain unclear. We hypothesized that remimazolam exerts anti‐inflammatory effects due to its antioxidant properties, which may affect the postoperative inflammatory response. This retrospective clinical study examined this hypothesis using laboratory and clinical approaches.

Methods

The antioxidant effects of remimazolam and dexmedetomidine were assessed by electron spin resonance (ESR) spectroscopy, and postoperative inflammatory responses were compared in 143 patients who underwent transcatheter aortic valve replacement at Kindai University Hospital between April 2021 and December 2022. The primary endpoint was the presence or absence of the antioxidant effects of the anesthetics themselves using ESR.

Results

Remimazolam at clinical concentrations exerted antioxidant effects, whereas dexmedetomidine did not. Increases in C‐reactive protein (CRP) levels on POD3 from preoperative values were significantly smaller in the remimazolam group than in the dexmedetomidine group (1.33 ± 1.29 vs. 2.17 ± 1.84, p = .014).

Conclusions

Remimazolam exerted stronger anti‐inflammatory effects than dexmedetomidine, and these effects were enhanced by its antioxidant properties, which may have affected postoperative CRP production.
Maternal screening for sexually transmitted infections in pregnant patients in low‐resource facilities: A call to action
Authors: Kway Venance Basil , Castillo Reyther Roberto Arturo , Rios Sauceda Cynthia Guadalupe , Castro Martinez Ilse Veronica
Published: March 2024

Synopsis

ASSURED criteria for POC test evaluation and rapid test analysis for STIs are discussed for cost‐effective screening, especially in low‐resource settings. Universal antepartum screening is advocated, with rapid tests as a viable option in low‐resource settings.
Association of long noncoding RNA H19 rs2839698 C/T with hepatitis B virus infection and hepatocellular carcinoma risk
Authors: Motawi Tarek K. , Mady Amira E. , Elhelbawy Mostafa , Talaat Roba M. , Shahin Nancy N.
Published: March 2024

The intricate pathogenesis of the hepatitis B virus (HBV) and its progression to hepatocellular carcinoma (HCC) have not yet been fully elucidated. H19 is one of the earliest imprinted long noncoding RNAs (lncRNAs) associated with liver pathobiology. This study investigated the association of H19 single nucleotide polymorphisms (SNPs) rs2839698 C/T and rs217727 C/T with HBV and HBV‐related HCC and their correlation with H19 expression level. A total of 230 subjects were enrolled in this study including 100 HBV‐infected patients, 30 HBV‐related HCC patients, and 100 apparently healthy controls. TaqMan genotyping human assays were utilized to assess allelic discrimination for H19 SNPs. H19 expression was assessed using quantitative real‐time polymerase chain reaction (qRT‐PCR). Our findings showed that H19 rs2839698 was linked to a higher incidence of HBV infection and HBV‐related HCC. Individuals who bear the CT genotype of rs2839698 were more susceptible to HBV infection (OR = 3.05; 95% CI 1.714–5.457; p < 0.001). Those harboring the TT genotype were more prone to develop HCC (OR = 2.625; 95% CI 1.037–6.64; p = 0.038). Our data revealed that rs2839698 could function as a promising predictor of HCC risk. Furthermore, H19 was significantly downregulated in HBV (p < 0.01) and HCC (p < 0.01) patients versus the control group. Significant upregulation of H19 in HCC patients with cirrhosis (p < 0.001) was detected. Altogether, this is considered the first prospective case‐control study to address the implication of the genetic variations of H19 SNPs in HBV and HBV‐related HCC in Egyptian patients.
HIF‐1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid‐induced osteonecrosis of the femoral head
Authors: Yu Yaling , Jiang Yixin , Ge Hongfan , Fan Xiaoli , Gao Hang , Zhou Zhenlei
Published: March 2024

With the prevalence of coronavirus disease 2019, the administration of glucocorticoids (GCs) has become more widespread. Treatment with high‐dose GCs leads to a variety of problems, of which steroid‐induced osteonecrosis of the femoral head (SONFH) is the most concerning. Since hypoxia‐inducible factor 1α (HIF‐1α) is a key factor in cartilage development and homeostasis, it may play an important role in the development of SONFH. In this study, SONFH models were established using methylprednisolone (MPS) in mouse and its proliferating chondrocytes to investigate the role of HIF‐1α in cartilage differentiation, extracellular matrix (ECM) homeostasis, apoptosis and glycolysis in SONFH mice. The results showed that MPS successfully induced SONFH in vivo and vitro, and MPS‐treated cartilage and chondrocytes demonstrated disturbed ECM homeostasis, significantly increased chondrocyte apoptosis rate and glycolysis level. However, compared with normal mice, not only the expression of genes related to collagens and glycolysis, but also chondrocyte apoptosis did not demonstrate significant differences in mice co‐treated with MPS and HIF‐1α inhibitor. And the effects observed in HIF‐1α activator‐treated chondrocytes were similar to those induced by MPS. And HIF‐1α degraded collagens in cartilage by upregulating its downstream target genes matrix metalloproteinases. The results of activator/inhibitor of endoplasmic reticulum stress (ERS) pathway revealed that the high apoptosis rate induced by MPS was related to the ERS pathway, which was also affected by HIF‐1α. Furthermore, HIF‐1α affected glucose metabolism in cartilage by increasing the expression of glycolysis‐related genes. In conclusion, HIF‐1α plays a vital role in the pathogenesis of SONFH by regulating ECM homeostasis, chondrocyte apoptosis, and glycolysis.
The presence of radiotoxic 210Po and 210Pb in Ukrainian wild medicinal plants and the assessment of related dose and cancer risk
Authors: Moniakowska A. , Konieczyński P. , Block K. , Lysiuk R. , Shapovalova N. , Strumińska‐Parulska D.
Published: March 2024

Herbal plants are considered natural pharmaceuticals but also accumulate chemical elements and compounds at high levels. 210Po and 210Pb are highly radiotoxic and may cause carcinogenesis due to ionizing radiation. Thirteen of the most popular wild‐growing herbaceous plant species, mostly included in the European Pharmacopoeia, were collected across Ukraine. 210Po and 210Pb were determined in the medicinal plants, and their radiotoxicity and cancer risk were calculated. The results of 210Po activities measured in herbal raw material ranged from 2.28 Bq kg−1 dw (where dw is dry weight) in herb of common horsetail (Equisetum arvense L.) collected near Lviv to 37.7 Bq kg−1 dw in leaves of common birch (Betula pendula Roth.) from Rava Ruska. The activity concentrations of 210Pb varied from 0.44 Bq kg−1 dw in leaves of common birch from Starokostyantyniv to 28.4 Bq kg−1 dw in leaves of common birch from Mizhhirya. There were statistically significant differences between 210Po and 210Pb content in flowers, leaves, and aerial portions. The studies indicated that the estimated annual effective radiation dose from Ukrainian herbs consumption was low, ranging 5.00–82.6 µSv from 210Po and 0.56–35.8 µSv from 210Pb, while the cancer morbidity and mortality risk ranged from 10−4 to 10−6. The presented data indicated no radiological risk related to using herbal plant materials.
Genetic counselors' and community clinicians' implementation and perceived barriers to informed consent during pre‐test counseling for hereditary cancer risk
Authors: Capasso Alexandra , Nehoray Bita , Gorman Nicholas , Quinn Emily A. , Bucio Daiana , Blazer Kathleen R.
Published: March 2024

As demand for genetic cancer risk assessment (GCRA) continues to increase, so does the sense of urgency to scale up efforts to triage patients, facilitate informed consent, and order genetic testing for cancer risk. The National Society of Genetic Counselors outlines the elements of informed consent that should be addressed in a GCRA session. While this practice resource aims to improve health equity, research on how well the elements of informed consent are implemented in practice is lacking. This retrospective and prospective mixed‐methods study assessed how adequately the elements of informed consent are addressed during pre‐test GCRA among 307 community clinicians (CC) and 129 cancer genetic counselors (GC), and barriers they face to addressing these elements. Results revealed that more than 90% of both cohorts consistently addressed components of at least 5 of the 10 elements of informed consent during a pre‐test consultation. Technical aspects and accuracy of the test and utilization of test results were the most similarly addressed elements. Notably, GCs more often review the purpose of the test and who to test, general information about the gene(s), and economic considerations whereas CCs more often review alternatives to testing. Both cohorts reported psychosocial aspects of the informed consent process as the least adequately addressed element. Time constraints and patient‐related concerns were most often cited by both cohorts as barriers to optimal facilitation of informed consent. Additional barriers reported by CCs included provider lack of awareness, experience, or education, and availability of resources and institutional support. Findings from this study may contribute to the development of alternative delivery models that incorporate supplementary educational tools to enhance patient understanding about the utility of genetic testing, while helping to mitigate the barrier of time constraints. Equally important is the use of this information to develop continuing education tools for providers.
High Torque teno virus load and outcome of patients undergoing allogeneic hematopoietic cell transplantation
Authors: Srour Micha , Grenier Corentin , Magro Leonardo , Hober Didier , Yakoub‐Agha Ibrahim , Engelmann Ilka
Published: March 2024

Quantification of Torque teno virus (TTV) load emerged as a marker of immunosuppression. Associations of TTV load with complications and survival after allogeneic hematopoietic cell transplantation (allo‐HCT) were controversial in published studies. In this prospective study, we aimed to identify factors influencing TTV load after allo‐HCT and to determine whether the TTV load is associated with complications or outcomes. Seventy allo‐HCT recipients were included. TTV DNA load was quantified in 469 plasma samples of 70 patients from Day (D) 15 before D120 after transplantation. The influence of transplant characteristics on TTV load and the associations of TTV load with viral infections, acute graft versus host disease, mortality, and relapse were analyzed. More than 80% of patients were TTV DNA positive from D30 after transplantation onwards. Median TTV load increased between D30 and D60 post‐transplantation. Patients with lymphoid malignancies had higher TTV load than those with myeloid malignancies. Myeloablative conditioning was associated with higher TTV loads. Patients with no measurable residual disease at transplant had higher TTV loads. High TTV load at D90 post‐transplantation was associated with lower overall survival and at D120 post‐transplantation was associated with higher relapse rate. In conclusion, TTV load at time points later than D90 after allo‐HCT may be useful to assess prognosis.
SIAH1 modulates antiviral immune responses by targeting deubiquitinase USP19
Authors: Weerawardhana Asela , Herath Thilina U. B. , Gayan Chathuranga W. A. , Kim Tae‐Hwan , Ekanayaka Pathum , Chathuranga Kiramage , Kang Ho‐Chul , Jung Jae U. , Lee Jong‐Soo
Published: March 2024

Tight control of the type I interferon (IFN) signaling pathway is critical for maintaining host innate immune responses, and the ubiquitination and deubiquitination of signaling molecules are essential for signal transduction. Deubiquitinase ubiquitin‐specific protein 19 (USP19) is known to be involved in deubiquitinating Beclin1, TRAF3, and TRIF for downregulation of the type I IFN signaling. Here, we show that SIAH1, a cellular E3 ubiquitin ligase that is involved in multicellular pathway, is a potent positive regulator of virus‐mediated type I IFN signaling that maintains homeostasis within the antiviral immune response by targeting USP19. In the early stages of virus infection, stabilized SIAH1 directly interacts with the USP19 and simultaneously mediates K27‐linked ubiquitination of 489, 490, and 610 residues of USP19 for proteasomal degradation. Additionally, we found that USP19 specifically interacts with MAVS and deubiquitinates K63‐linked ubiquitinated MAVS for negative regulation of type I IFN signaling. Ultimately, we identified that SIAH1‐mediated degradation of USP19 reversed USP19‐mediated deubiquitination of MAVS, Beclin1, TRAF3, and TRIF, resulting in the activation of antiviral immune responses. Taken together, these findings provide new insights into the molecular mechanism of USP19 and SIAH1, and suggest a critical role of SIAH1 in antiviral immune response and homeostasis.
UMP‐CMP kinase 2 inhibits ZIKV replication through activation of type I IFN signaling pathway
Authors: Zhu Ya , Tan Qi , Shi Yaoqiang , Li Qingyuan , Li Shilin , Wen Wenxian , Xie He , Li Bin , Duan Xiaoqiong , Chen Limin
Published: March 2024

Cytidine/uridine monophosphate kinase 2 (UMP‐CMP kinase 2, CMPK2) has been reported as an antiviral interferon‐stimulated gene (ISG). We previously observed that the expression of CMPK2 was significantly upregulated after Zika Virus (ZIKV) infection in A549 cells. However, the association and the underlying mechanisms between CMPK2 induction and ZIKV replication remain to be determined. We investigated the induction of CMPK2 during ZIKV infection and the effect of CMPK2 on ZIKV replication in A549, U251, Vero, IFNAR‐deficient U5A and its parental 2fTGH cells, Huh7 and its RIG‐I‐deficient derivatives Huh7.5.1 cells. The activation status of Jak‐STAT signaling pathway was determined by detecting the phosphorylation level of STAT1, the activity of interferon stimulated response element (ISRE) and the expression of several interferon stimulated genes (ISGs). We found that ZIKV infection induced CMPK2 expression through an IFNAR and RIG‐I dependent manner. Overexpression of CMPK2 inhibited while CMPK2 knockdown promoted ZIKV replication in A549 and U251 cells. Mechanically, we found that CMPK2 overexpression increased IFNβ expression and activated Jak/STAT signaling pathway as shown by the increased level of p‐STAT1, enhanced activity of ISRE, and the upregulated expression of downstream ISGs. These findings suggest that ZIKV infection induced CMPK2 expression, which inhibited ZIKV replication and serves as a positive feedback regulator for IFN‐Jak/STAT pathway.