bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional expression of FumA in
Aspergillus niger
enhances synthesis of L-malic acid
Authors: Zhang Chi , Shi Man , Xu Yingyan , Yang Dongdong , Lu Ling , Xue Feng , Xu Qing 
Published: March 2024

ABSTRACT

Currently, the L-malic acid titer achieved through
Aspergillus niger
fermentation reaches 201 g/L, meeting industrial demands satisfactorily. However, the co-presence of structurally similar fumaric acid and succinic acid in fermentation products suggests a theoretical potential for further improvement in L-malic acid production. In the tricarboxylic acid cycle, fumarate reductase mediates the conversion of succinic acid to fumaric acid. Subsequently, fumarase catalyzes the conversion of fumaric acid to L-malic acid. Notably, both enzymatic reactions are reversible. Our investigation revealed that
A. niger
contains only one mitochondria-located fumarase FumA. Employing CRISPR-Cas9 technology, we performed a replacement of the
fumA
promoter with a doxycycline-induced promoter Tet. Under non-inducing condition, the conditional strain exhibited increased levels of fumaric acid and succinic acid. It strongly suggests that FumA mainly promotes the flow of fumaric acid to L-malic acid. Furthermore, a promoter PmfsA that is exclusively activated in a fermentation medium by calcium carbonate was identified through RNA-sequencing screening. Utilizing PmfsA to regulate
fumA
expression led to a 9.0% increase in L-malic acid titer, an 8.75% increase in yield (glucose to L-malic acid), and an 8.86% enhancement in productivity. This research serves as a significant step toward expediting the industrialization of L-malic acid synthesis via biological fermentation. Additionally, it offers valuable insights for the biosynthesis of other organic acids.

IMPORTANCE

This study focuses on enhancing L-malic acid synthesis by modifying the tricarboxylic acid cycle within the mitochondria of
Aspergillus niger
. We emphasize the significant role of fumarase in converting fumaric acid into L-malic acid, enhancing our understanding of metabolic pathways in
A. niger
. The precise regulation of
fumA
is highlighted as a key factor in enhancing L-malic acid production. Furthermore, this research introduces a stringent conditional promoter (PmfsA), exclusively activated by CaCO
3
. The utilization of PmfsA for
fumA
expression resulted in heightened L-malic acid titers. The progress in metabolic engineering and bioprocess optimization holds promise for expediting industrial L-malic acid synthesis via biological fermentation. Moreover, it carries implications for the biosynthesis of various other organic acids.
Supplemental Material: Foreland basin development in response to Proto-Tethyan Ocean closure, western North China Block
Authors: Sun Jiaopeng , Dong Yunpeng 
Published: March 2024

<p>Figure S1: Representative photomicrographs (cross-polarized light) of Cambrian and Ordovician samples selected for detrital zircon U-Pb geochronology. Figure S2: Representative cathodoluminescence images of zircons analyzed from Cambrian and Ordovician samples. Table S1: Laser ablation–inductively coupled plasma–mass spectrometry data of detrital zircons from the Cambrian and Ordovician sandstones from eastern Qilian Orogen and western North China Block. </p>
Visual acuity and visual field as a function of disease duration in patients with birdshot chorioretinitis
Authors: Loeliger Jordan , Monnet Dominique , Thorne Jennifer , Imikerene Linda , Kecili Souhila , Brézin Antoine P 
Published: March 2024

Background
Birdshot chorioretinitis (BSCR) is a chronic bilateral posterior uveitis, which can affect central as well as peripheral vision. The aim of this study was to assess how visual acuity and visual field evolved over time in patients with BSCR.

Methods
This was a prospective, observational, single-centre study based on data from the CO-BIRD cohort. Patient visits were categorised based on the time elapsed since the first symptoms, and groups of patients with different disease duration were defined. The main outcome measures were the best corrected visual acuity (BCVA), the mean deviation (MD) and the standard pattern deviation (PSD).

Results
The study included 447 Caucasian patients (181 males and 266 females), all of whom HLA-A29 carriers. From onset to 30 years of disease duration, the number of patients in each consecutive 5-year period was 237, 250, 196, 147, 78 and 32, respectively. Overall, the range of visual acuity and visual field results increased with disease duration. BCVA gradually decreased and showed a significant decline after 11–15 years after the first symptoms. Among the visual field indices, PSD significantly increased after 16–20 years, while MD showed a significant decline after 21–25 years. No major gender differences were found in visual outcomes, indicating comparable severity. The intereye correlations of MD and PSD were stronger than those of BCVA.

Conclusions
BSCR resulted in a large heterogeneity of visual outcomes, which increased with time. Our data provide an overview of the visual consequences of BSCR as a function of disease duration.
Potential smoke-free dividend across local areas in England: a cross-sectional analysis
Authors: Morris Damon , Gillespie Duncan , Dockrell Martin J , Cook Mark , Horton Marie , Brown Jamie , Langley Tessa Elisabeth 
Published: March 2024

BackgroundThe value that might be added to local economies each year through the money that people who smoke tobacco would save if everyone quit smoking is called the ‘smoke-free dividend’. This study aimed to estimate the value of the smoke-free dividend across local areas in England, and how it relates to the average income in those areas.MethodsThe study was a cross-sectional descriptive analysis of tobacco expenditure from the Smoking Toolkit Study (STS) matched to income and smoking prevalence data for English local authorities. The STS sample was from 2014 to 2020 and comprised 18 721 adults who smoke cigarettes. Self-reported expenditure estimates from the STS were adjusted for under-reporting. This adjustment aimed to align the total expenditure estimate with figures derived from government tax receipts and national estimates of illicit tobacco use. The smoke-free dividend is calculated as 93% of spending on legal tobacco, which is the percentage estimated to leave the local economy, plus 100% of spending on illicit tobacco.ResultsThe total dividend in England is estimated to be £10.9 billion each year, which equates to £1776 per person who smokes or £246 per adult regardless of smoking status. The estimated dividend is greater in areas with lower average income, with a correlation coefficient of −0.521 (95% CI −0.629, –0.392) between the average income of local areas and the dividend per adult.ConclusionsThis study has estimated that local economies could gain a substantial dividend if everybody stopped smoking, which is larger in lower income areas, meaning that geographical economic inequalities could be reduced.
Identification of Enhanced Vaccine Mimotopes for the p15E Murine Cancer Antigen
Authors: Zhou Shiqi , Song Yiting , Luo Yuan , Quinn Breandan , Jiao Yang , Long Mark D. , Abrams Scott I. , Lovell Jonathan F. 
Published: March 2024

Abstract

Mimotopes of short CD8+ T-cell epitopes generally comprise one or more mutated residues, and can increase the immunogenicity and function of peptide cancer vaccines. We recently developed a two-step approach to generate enhanced mimotopes using positional peptide microlibraries and herein applied this strategy to the broadly used H-2Kb–restricted murine leukemia p15E tumor rejection epitope. The wild-type p15E epitope (sequence: KSPWFTTL) was poorly immunogenic in mice, even when combined with a potent peptide nanoparticle vaccine system and did not delay p15E-expressing MC38 tumor growth. Following positional microlibrary functional screening of over 150 mimotope candidates, two were identified, both with mutations at residue 3 (p15E-P3C; “3C,” and p15E-P3M; “3M”) that better induced p15E-specific CD8+ T cells and led to tumor rejection. Although 3M was more immunogenic, 3C effectively delayed tumor growth in a therapeutic setting relative to the wild-type p15E. As 3C had less H-2Kb affinity relative to both p15E and 3M, 15 additional mimotope candidates (all that incorporated the 3C mutation) were assessed that maintained or improved predicted MHC-I affinity. Valine substitution at position 2 (3C2V, sequence: KVCWFTTL) led to improved p15E-specific immunogenicity, tumor rejection, and subsequent long-term antitumor immunity. 3C, 3M, and 3C2V mimotopes were more effective than p15E in controlling MC38 and B16-F10 tumors. T-cell receptor (TCR) sequencing revealed unique TCR transcripts for mimotopes, but there were no major differences in clonality. These results provide new p15E mimotopes for further vaccine use and illustrate considerations for MHC-I affinity, immunogenicity, and functional efficacy in mimotope design.

Significance:
The MHC-I–restricted p15E tumor rejection epitope is expressed in multiple murine cancer lines and is used as a marker of antitumor cellular immunity, but has seen limited success as a vaccine immunogen. An in vivo screening approach based on a positional peptide microlibraries is used to identify enhanced p15E mimotopes bearing amino acid mutations that induce significantly improved functional immunogenicity relative to vaccination with the wild-type epitope.
A Comparison of the Impacts of Two Consecutive Double-Peaked La Niña Events on Antarctic Sea Ice in Austral Spring
Authors: Zhang Chao , Li Shuanglin , Han Zhe 
Published: March 2024

Abstract
Among nine La Niña events since 1980, there are seven double-peaked La Niña events that typically persist for 2 years and peak twice in the two consecutive boreal winters. In the study, the individual impacts of the first and second peak episodes of such La Niña on the Antarctic sea ice in austral spring (September–November) were compared. The results suggest a difference. The first episode induces a tripolar distribution of sea ice concentration (SIC) with a negative anomaly in the Bellingshausen Sea sandwiched with positive anomalies in the Ross Sea and the northeastern Weddell Sea. The second causes an SIC reduction in most parts of the Southern Ocean except for the eastern Ross–western Amundsen Seas where an increase is observed. Mechanistically, the first episode forces one single Rossby wave train to propagate southeastward, causing a strong cyclone anomaly over the eastern Ross–Amundsen–Bellingshausen Seas along with a weak anticyclone over the Weddell Sea. In comparison, the second La Niña excites two branches of Rossby wave trains emanating from the southeastern tropical Indian Ocean and the central equatorial Pacific, respectively, which induce three anomalous anticyclones and two anomalous cyclones over the Southern Ocean. These different atmospheric circulation anomalies shape their different sea ice distributions between the two La Niña episodes through both dynamic and thermodynamic processes. The modeling results from CAM5 verify these differences.

Significance Statement
Under global warming, the double-peaked La Niña occurs more frequently. The first and second La Niña episodes in such double-peaked La Niña are distinct from each other not only in their onset and developing mechanisms but also in their climate impacts. Based on observational analyses and model experiments, the study investigated the distinctive impacts of the first and second episodes on the austral spring Antarctic sea ice. The results reveal that the first episode excites one single southeastward-propagated Rossby wave train, while the second episode forces two branches of Rossby wave trains. These different atmospheric responses in the Southern Hemisphere shape the distinct sea ice distributions both dynamically and thermodynamically. The study also indicates the diversity of tropical–Antarctic teleconnections.
Peroneus Brevis to Longus Tendon Transfer in the Treatment of Flexible Progressive Collapsing Foot Deformity: A Cadaveric Study
Authors: Conti Matthew S. , Kim Jaeyoung , Hoffman Jeffrey , Jones Carroll P. , Ellis Scott J. , Deland Jonathan T. , Steineman Brett 
Published: March 2024

Background: Although operative treatment of the flexible progressive collapsing foot deformity (PCFD) remains controversial, correction of residual forefoot varus and stabilization of the medial column are important components of reconstruction. A peroneus brevis (PB) to peroneus longus (PL) tendon transfer has been proposed to address these deformities. The aim of our study was to determine the effect of an isolated PB-to-PL transfer on medial column kinematics and plantar pressures in a simulated PCFD (sPCFD) cadaveric model. Methods: The stance phase of level walking was simulated in 10 midtibia cadaveric specimens using a validated 6–degree of freedom robot. Bone motions and plantar pressure were collected in 3 conditions: intact, sPCFD, and after PB-to-PL transfer. The PB-to-PL transfer was performed by transecting the PB and advancing the proximal stump 1 cm into the PL. Outcome measures included the change in joint rotation of the talonavicular, first naviculocuneiform, and first tarsometatarsal joints between conditions. Plantar pressure outcome measures included the maximum force, peak pressure under the first metatarsal, and the lateral-to-medial forefoot average pressure ratio. Results: Compared to the sPCFD condition, the PB-to-PL transfer resulted in significant increases in talonavicular plantarflexion and adduction of 68% and 72%, respectively, during simulated late stance phase. Talonavicular eversion also decreased in simulated late stance by 53%. Relative to the sPCFD condition, the PB-to-PL transfer also resulted in a 17% increase ( P = .045) in maximum force and a 45-kPa increase ( P = .038) in peak pressure under the first metatarsal, along with a medial shift in forefoot pressure. Conclusion: The results from this cadaver-based simulation suggest that the addition of a PB-to-PL transfer as part of the surgical management of the flexible PCFD may aid in correction of deformity and increase the plantarflexion force under the first metatarsal. Clinical Relevance: This study provides biomechanical evidence to support the addition of a PB-to-PL tendon transfer in the surgical treatment of flexible PCFD.
The use of a digital life story to support person-centred care of older adults with dementia: A scoping review
Authors: Dellkvist Helén , Dallora Ana Luiza , Christiansen Line , Skär Lisa 
Published: March 2024

IntroductionA life story (LS) is a tool healthcare professionals (HCPs) use to help older adults with dementia preserve their identities by sharing their stories. Applied health technology can be considered a niche within welfare technology. Combining technology and nursing, such as using life stories in digital form, may support person-centred care and allow HCPs to see the person behind the disease.ObjectiveThe study's objective was to summarise and describe the use of life stories in digital form in the daily care of older adults with dementia.MethodsA scoping review was conducted in five stages. Database searches were conducted in Cinahl, PubMed, Scopus, Web of Science, and Google Scholar; 31 articles were included. A conventional qualitative content analysis of the collected data was conducted.ResultsThe qualitative analysis resulted in three categories: (1) benefits for older adults, (2) influence on HCPs’ work, and (3) obstacles to implementing a digital LS in daily care.ConclusionOlder adults with dementia can receive person-centred care through a digital LS based on their wishes. A digital LS can enable symmetric communication and serve as an intergenerational communication tool. It can be used to handle behavioural symptoms. Using a digital LS in the later stages of dementia may differ from using it earlier in dementia. However, it may compensate for weakening abilities in older adults by enhancing social interaction.
A review: Exposure to bisphenol a analogues in non-human primates as a potential cause of endometriosis
Authors: Apiyo Oreng’ P , Nyachieo Atunga , Juma Almas R , Mutai Ivy J , Mwethera Peter G , Mecha Ezekiel O , Omwandho Charles OA , Kiesel Ludwig , Götte Martin , Muteshi Charles , Obiero Jael A 
Published: March 2024

Introduction: Bisphenol A is a synthetic compound widely used in the production of polycarbonate plastics and epoxy resins worldwide. As an environmental toxin, it has been reported in plastic equipment and utensils, water bottles and bottle tops, water supply pipes and epoxy resins that coat most of the metal food cans. It is a known endocrine-disrupting chemical and has been progressively replaced by its derivatives including bisphenol S, bisphenol F, bisphenol E, bisphenol AF, bisphenol B and tetramethyl bisphenol F. Bisphenol A and its analogues can bind to estrogen receptors and trigger multiple cellular responses at the organism level. Methods: A comprehensive literature review was done utilising electronic databases of PubMed, Google Scholar, Hinari, Connected papers and Science Direct from 1991 onwards. The articles were only included if they reported original relevant research and were limited to articles written in English. Results: Animal models, including non-human primates, have been used to study their effects on the endocrine system. Its endocrine disruption activity is reported to be the most studied effect in reproductive biology indicating that it may potentially cause endometriosis in females. Though non-human primates are closely related to humans, limited data exists on their associations between Bisphenol A exposure and its analogues and the pathophysiology of endometriosis. Conclusion: Given the current multifaceted knowledge/theory on endometriosis etiology, there is a strong necessity to conduct further biomedical research that utilises non-human primates to study the link between endocrine-disrupting chemicals and its effects on endometriosis.
Determinants influencing implementation of clinical risk management – Qualitative results of a national survey among clinical risk managers in Germany (KHaSiMiR21)
Authors: Roesner Hannah , Blum Karl , Gambashidze Nikoloz , Schmiedhofer Martina , Weigl Matthias , Strametz Reinhard 
Published: March 2024

Background The improvement of patient safety requires management of clinical risks in hospitals. However, implementation status of clinical risk management (CRM) varies substantially across hospitals. Investigations into facilitators and barriers for effective implementation are thus necessary. Using an in-depth interview study with CRM experts in hospitals, this study aimed to investigate factors accountable for effective development and implementation status of CRM measures in Germany. Methods As part of a nationwide survey, we conducted semi-standardized interviews with n = 10 selected clinical risk managers from general hospitals. We used qualitative content analysis to identify barriers and facilitators to the implementation of CRM. Results A broad range of determinants influencing CRM implementation were identified. Determinants were categorized into five thematic categories: general knowledge of CRM, safety culture, availability of resources, multi-level engagement and organizational structures. Discussion While numerous barriers to CRM implementation were identified, interviewees reported only a few supporting factors in comparison. Results suggest further challenges in effective CRM implementation and inform future research and implementation efforts.
Targeting myeloperoxidase to stabilize unruptured aneurysm: an imaging-guided approach
Authors: Shi Xingchi , Xue Yuan , Wu Huiyu , Shen Chengyi , Zhong Lei , Lei Jun , Xia Zhiyang , Yang Ying , Zhu Jiang 
Published: March 2024

AbstractInflammation plays a key role in pathogenesis and rupture of aneurysms. Non-invasively and dynamically monitoring aneurysm inflammation is critical. This study evaluated myeloperoxidase (MPO) as an imaging biomarker and therapeutic target for aneurysm inflammation using an elastase-induced rabbit model treated with or without 4-aminobenzoic acid hydrazide (ABAH), an irreversible inhibitor of MPO. Myeloperoxidase-sensitive magnetic resonance imaging (MRI) using Mn-TyrEDTA, a peroxidase activity-dependent contrast agent, revealed weak contrast enhancement in contralateral arteries and decreased contrast enhancement in aneurysm walls with ABAH treatment, indicating MPO activity decreased and inflammation mitigated. This was supported by reduced immune cell infiltration, matrix metalloproteinases (MMP-2 and − 9) activity, ROS production and arterial wall destruction on histology. Finally, the aneurysm expansion rate remained < 50% throughout the study in the ABAH(+) group, but increased gradually in the ABAH(-) group. Our results suggest that inhibition of MPO attenuated inflammation and expansion of experimental aneurysm and MPO-sensitive MRI showed promise as a noninvasive tool for monitoring aneurysm inflammation.
Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway
Authors: Guo Manliang , Li Shiqi , Li Chuan , Mao Xueyan , Tian Liru , Yang Xintong , Xu Caixia , Zeng Mian 
Published: March 2024

Abstract
Background
Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has been reported that Wnt5a shows protective effects on endothelial cells. Therefore, the study aimed to investigate whether overexpression of Wnt5a could promote the protective effects of MSCs on Lipopolysaccharide (LPS)-induced endothelial cell injury.

Methods
To evaluate the protective effects of MSCs overexpressing Wnt5a, we assessed the migration, proliferation, apoptosis, and angiogenic ability of endothelial cells. We assessed the transcription of protective cellular factors using qPCR and determined the molecular mechanism using Western blot analysis.

Results
Overexpression of Wnt5a upregulated the transcription of protective cellular factors in MSCs. Co-culture of MSCWnt5a promoted endothelial migration, proliferation and angiogenesis, and inhibited endothelial cell apoptosis through the PI3K/AKT pathway.

Conclusions
Overexpression of Wnt5a promoted the therapeutic effect of MSCs on endothelial cell injury through the PI3K/AKT signaling. Our study provides a novel approach for utilizing genetically modified MSCs in the transplantation therapy for ARDS.