bluuebunny/crossref_metadata_2025 huggingface dataset:
Four Decades of Carrier Detection and Prenatal Diagnosis in Hemophilia A: Historical Overview, State of the Art and Future Directions
Authors: Dardik Rima , Janczar Szymon , Lalezari Shadan , Avishai Einat , Levy-Mendelovich Sarina , Barg Assaf Arie , Martinowitz Uri , Babol-Pokora Katarzyna , Mlynarski Wojciech , Kenet Gili
Published: July 2023

Hemophilia A (HA), a rare recessive X-linked bleeding disorder, is caused by either deficiency or dysfunction of coagulation factor VIII (FVIII) resulting from deleterious mutations in the F8 gene encoding FVIII. Over the last 4 decades, the methods aimed at determining the HA carrier status in female relatives of HA patients have evolved from phenotypic studies based on coagulation tests providing merely probabilistic results, via genetic linkage studies based on polymorphic markers providing more accurate results, to next generation sequencing studies enabling highly precise identification of the causative F8 mutation. In parallel, the options for prenatal diagnosis of HA have progressed from examination of FVIII levels in fetal blood samples at weeks 20–22 of pregnancy to genetic analysis of fetal DNA extracted from chorionic villus tissue at weeks 11–14 of pregnancy. In some countries, in vitro fertilization (IVF) combined with preimplantation genetic diagnosis (PGD) has gradually become the procedure of choice for HA carriers who wish to prevent further transmission of HA without the need to undergo termination of pregnancies diagnosed with affected fetuses. In rare cases, genetic analysis of a HA carrier might be complicated by skewed X chromosome inactivation (XCI) of her non-hemophilic X chromosome, thus leading to the phenotypic manifestation of moderate to severe HA. Such skewed XCI may be associated with deleterious mutations in X-linked genes located on the non-hemophilic X chromosome, which should be considered in the process of genetic counseling and PGD planning for the symptomatic HA carrier. Therefore, whole exome sequencing, combined with X-chromosome targeted bioinformatic analysis, is highly recommended for symptomatic HA carriers diagnosed with skewed XCI in order to identify additional deleterious mutations potentially involved in XCI skewing. Identification of such mutations, which may profoundly impact the reproductive choices of HA carriers with skewed XCI, is extremely important.
Transient Receptor Potential Ankyrin 1 (TRPA1) Channel Mediates Acrolein Cytotoxicity in Human Lung Cancer Cells
Authors: Sakamoto Akihiko , Terui Yusuke , Igarashi Kazuei , Kashiwagi Keiko
Published: July 2023

Transient receptor potential ankyrin 1 (TRPA1) is a nonselective ion channel implicated in thermosensation and inflammatory pain. It has been reported that expression of the TRPA1 channel is induced by cigarette smoke extract. Acrolein found in cigarette smoke is highly toxic and known as an agonist of the TRPA1 channel. However, the role of TRPA1 in the cytotoxicity of acrolein remains unclear. Here, we investigated whether the TRPA1 channel is involved in the cytotoxicity of acrolein in human lung cancer A549 cells. The IC50 of acrolein in A549 cells was 25 μM, and acrolein toxicity increased in a concentration- and time-dependent manner. When the effect of acrolein on TRPA1 expression was examined, the expression of TRPA1 in A549 cells was increased by treatment with 50 μM acrolein for 24 h or 500 μM acrolein for 30 min. AP-1, a transcription factor, was activated in the cells treated with 50 μM acrolein for 24 h, while induction of NF-κB and HIF-1α was observed in the cells treated with 500 μM acrolein for 30 min. These results suggest that acrolein induces TRPA1 expression by activating these transcription factors. Overexpression of TRPA1 in A549 cells increased acrolein sensitivity and the level of protein-conjugated acrolein (PC-Acro), while knockdown of TRPA1 in A549 cells or treatment with a TRPA1 antagonist caused tolerance to acrolein. These findings suggest that acrolein induces the TRPA1 channel and that an increase in TRPA1 expression promotes the cytotoxicity of acrolein.
Phytochemical Screening of Ultrasonic Extracts of Salix Species and Molecular Docking Study of Salix-Derived Bioactive Compounds Targeting Pro-Inflammatory Cytokines
Authors: Gligorić Emilia , Igić Ružica , Teofilović Branislava , Grujić-Letić Nevena
Published: July 2023

Willow bark (Salix spp., Salicaceae) is a traditional analgesic and antirheumatic herbal medicine. The aim of this study was to evaluate and compare the phytochemical and antioxidant profiles of leaf and bark extracts of six species of the genus Salix obtained by ultrasound-assisted extraction (UAE) and to examine the inhibitory potential of target bioactive compounds against two inflammatory mediators, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), through in silico molecular docking. The total phenolic and flavonoid content of the extracts was estimated using spectrophotometric methods and the antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and hydroxyl radical (•OH) scavenging assays. Chemical profiling of extracts was carried out using high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD). Principal component analysis (PCA) was performed to differentiate the sample extracts based on their phytochemical profiles and amounts of target bioactive compounds. Chemical composition varied among the analyzed willow species and also among the plant organs of the same species. The major bioactive compounds of the extracts were salicin, chlorogenic acid, rutin and epicatechin. The extracts exhibited significant DPPH● and ●OH scavenging activities. Results of molecular docking revealed that chlorogenic acid had the highest binding affinity toward TNF-α and IL-6. UAE extracts represent valuable sources of antioxidant and anti-inflammatory compounds.
How Can the Microbiome Induce Carcinogenesis and Modulate Drug Resistance in Cancer Therapy?
Authors: Mendes Inês , Vale Nuno
Published: July 2023

Over the years, cancer has been affecting the lives of many people globally and it has become one of the most studied diseases. Despite the efforts to understand the cell mechanisms behind this complex disease, not every patient seems to respond to targeted therapies or immunotherapies. Drug resistance in cancer is one of the limiting factors contributing to unsuccessful therapies; therefore, understanding how cancer cells acquire this resistance is essential to help cure individuals affected by cancer. Recently, the altered microbiome was observed to be an important hallmark of cancer and therefore it represents a promising topic of cancer research. Our review aims to provide a global perspective of some cancer hallmarks, for instance how genetic and epigenetic modifications may be caused by an altered human microbiome. We also provide information on how an altered human microbiome can lead to cancer development as well as how the microbiome can influence drug resistance and ultimately targeted therapies. This may be useful to develop alternatives for cancer treatment, i.e., future personalized medicine that can help in cases where traditional cancer treatment is unsuccessful.
Gender-Specific Differences in Human Vertebral Bone Marrow Clot
Authors: Salamanna Francesca , Contartese Deyanira , Borsari Veronica , Pagani Stefania , Sartori Maria , Tschon Matilde , Griffoni Cristiana , Giavaresi Gianluca , Tedesco Giuseppe , Barbanti Brodano Giovanni , Gasbarrini Alessandro , Fini Milena
Published: July 2023

Recently, our group described the application of vertebral bone marrow (vBMA) clot as a cell therapy strategy for spinal fusion. Its beneficial effects were confirmed in aging-associated processes, but the influence of gender is unknown. In this study, we compared the biological properties of vBMA clots and derived vertebral mesenchymal stem cells (MSCs) from female and male patients undergoing spinal fusion procedures and treated with vBMA clot. We analyzed the expression of growth factors (GFs) in vBMA clots and MSCs as well as morphology, viability, doubling time, markers expression, clonogenicity, differentiation ability, senescence factors, Klotho expression, and HOX and TALE gene profiles from female and male donors. Our findings indicate that vBMA clots and derived MSCs from males had higher expression of GFs and greater osteogenic and chondrogenic potential compared to female patients. Additionally, vBMA-clot-derived MSCs from female and male donors exhibited distinct levels of HOX and TALE gene expression. Specifically, HOXA1, HOXB8, HOXD9, HOXA11, and PBX1 genes were upregulated in MSCs derived from clotted vBMA from male donors. These results demonstrate that vBMA clots can be effectively used for spinal fusion procedures; however, gender-related differences should be taken into consideration when utilizing vBMA-clot-based studies to optimize the design and implementation of this cell therapy strategy in clinical trials.
Endoreplication—Why Are We Not Using Its Full Application Potential?
Authors: Kołodziejczyk Izabela , Tomczyk Przemysław , Kaźmierczak Andrzej
Published: July 2023

Endoreplication—a process that is common in plants and also accompanies changes in the development of animal organisms—has been seen from a new perspective in recent years. In the paper, we not only shed light on this view, but we would also like to promote an understanding of the application potential of this phenomenon in plant cultivation. Endoreplication is a pathway for cell development, slightly different from the classical somatic cell cycle, which ends with mitosis. Since many rounds of DNA synthesis take place within its course, endoreplication is a kind of evolutionary compensation for the relatively small amount of genetic material that plants possess. It allows for its multiplication and active use through transcription and translation. The presence of endoreplication in plants has many positive consequences. In this case, repeatedly produced copies of genes, through the corresponding transcripts, help the plant acquire the favorable properties for which proteins are responsible directly or indirectly. These include features that are desirable in terms of cultivation and marketing: a greater saturation of fruit and flower colors, a stronger aroma, a sweeter fruit taste, an accumulation of nutrients, an increased resistance to biotic and abiotic stress, superior tolerance to adverse environmental conditions, and faster organ growth (and consequently the faster growth of the whole plant and its biomass). The two last features are related to the nuclear-cytoplasmic ratio—the greater the content of DNA in the nucleus, the higher the volume of cytoplasm, and thus the larger the cell size. Endoreplication not only allows cells to reach larger sizes but also to save the materials used to build organelles, which are then passed on to daughter cells after division, thus ending the classic cell cycle. However, the content of genetic material in the cell nucleus determines the number of corresponding organelles. The article also draws attention to the potential practical applications of the phenomenon and the factors currently limiting its use.
Liver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications
Authors: Kaps Leonard , Limeres María José , Schneider Paul , Svensson Malin , Zeyn Yanira , Fraude Silvia , Cacicedo Maximiliano L. , Galle Peter R. , Gehring Stephan , Bros Matthias
Published: July 2023

Hepatocytes exert pivotal roles in metabolism, protein synthesis and detoxification. Non-parenchymal liver cells (NPCs), largely comprising macrophages, dendritic cells, hepatic stellate cells and liver sinusoidal cells (LSECs), serve to induce immunological tolerance. Therefore, the liver is an important target for therapeutic approaches, in case of both (inflammatory) metabolic diseases and immunological disorders. This review aims to summarize current preclinical nanodrug-based approaches for the treatment of liver disorders. So far, nano-vaccines that aim to induce hepatitis virus-specific immune responses and nanoformulated adjuvants to overcome the default tolerogenic state of liver NPCs for the treatment of chronic hepatitis have been tested. Moreover, liver cancer may be treated using nanodrugs which specifically target and kill tumor cells. Alternatively, nanodrugs may target and reprogram or deplete immunosuppressive cells of the tumor microenvironment, such as tumor-associated macrophages. Here, combination therapies have been demonstrated to yield synergistic effects. In the case of autoimmune hepatitis and other inflammatory liver diseases, anti-inflammatory agents can be encapsulated into nanoparticles to dampen inflammatory processes specifically in the liver. Finally, the tolerance-promoting activity especially of LSECs has been exploited to induce antigen-specific tolerance for the treatment of allergic and autoimmune diseases.
The Evaluation of Rac1 Signaling as a Potential Therapeutic Target of Alzheimer’s Disease
Authors: Wang Huanhuan , Yamahashi Yukie , Riedl Marcel , Amano Mutsuki , Kaibuchi Kozo
Published: July 2023

The Small GTPase Rac1 is critical for various fundamental cellular processes, including cognitive functions. The cyclical activation and inactivation of Rac1, mediated by Rac guanine nucleotide exchange factors (RacGEFs) and Rac GTPase-activating proteins (RacGAPs), respectively, are essential for activating intracellular signaling pathways and controlling cellular processes. We have recently shown that the Alzheimer’s disease (AD) therapeutic drug donepezil activates the Rac1-PAK pathway in the nucleus accumbens (NAc) for enhanced aversive learning. Also, PAK activation itself in the NAc enhances aversive learning. As aversive learning allows short-term preliminary AD drug screening, here we tested whether sustained Rac1 activation by RacGAP inhibition can be used as an AD therapeutic strategy for improving AD-learning deficits based on aversive learning. We found that the RacGAP domain of breakpoint cluster region protein (Bcr) (Bcr-GAP) efficiently inhibited Rac1 activity in a membrane ruffling assay. We also found that, in striatal/accumbal primary neurons, Bcr knockdown by microRNA mimic-expressing adeno-associated virus (AAV-miRNA mimic) activated Rac1-PAK signaling, while Bcr-GAP-expressing AAV inactivated it. Furthermore, conditional knockdown of Bcr in the NAc of wild-type adult mice enhanced aversive learning, while Bcr-GAP expression in the NAc inhibited it. The findings indicate that Rac1 activation by RacGAP inhibition enhances aversive learning, implying the AD therapeutic potential of Rac1 signaling.
Preoperative and Postoperative Kinesiophobia Influences Postoperative Outcome Measures Following Anterior Cruciate Ligament Reconstruction: A Prospective Study
Authors: Longo Umile Giuseppe , Marino Martina , Rizzello Giacomo , De Salvatore Sergio , Piergentili Ilaria , Denaro Vincenzo
Published: July 2023

The anterior cruciate ligament (ACL) is the most injured ligament of the knee, and the treatment of choice is usually ACL reconstruction. Kinesiophobia refers to an irrational and paralyzing fear of movement caused by the feeling of being prone to injury or reinjury. The aim of the present study is to evaluate the relationship between preoperative and postoperative kinesiophobia with postoperative outcomes of ACL-R evaluated through SF-36, ACL-RSI, KOOS, and OKS scores. Included patients all underwent ACL reconstruction. The preoperative TSK-13 questionnaire and six-month postoperative TSK-13, ACL-RSI, SF-36, KOOS, and OKS questionnaires were assessed in included patients. Normal distribution was assessed using the Shapiro–Wilk test. The study included 50 patients who filled out the questionnaires at the 6-month postoperative follow-up. Correlations between preoperative TSK-13 and postoperative outcome measures revealed a low–moderate negative correlation between preoperative TSK-13 and SF-36 PCS at 6-month follow-up. Correlations between postoperative TSK-13 and postoperative outcome measures revealed a high negative correlation between preoperative TSK-13 and ACL-RSI, KOOS Symptoms, KOOS Pain, KOOS ADL, and OKS at 6-month follow-up. Preoperative and postoperative kinesiophobia were found to influence postoperative ACL-R outcomes negatively, more specifically an increase in kinesiophobia showed a statistically significant correlation with worse postoperative SF-36 PCS scores in patients.
Prevalence of Geographic Atrophy in Advanced Age-Related Macular Degeneration (AMD) in Daily Practice
Authors: Abdin Alaa Din , Devenijn Machteld , Fulga Roxana , Langenbucher Achim , Seitz Berthold , Kaymak Hakan
Published: July 2023

Purpose: To investigate the prevalence of geographic atrophy (GA) in advanced age-related macular degeneration (AMD) and the proportion of eyes that would meet the indication criteria for treatment with the first intravitreal anti-C3 agent (pegcetacoplan). Methods: This retrospective cross-sectional study included all AMD patients who visited the Macular-Retina-Centre Oberkassel in 2021. Eyes were classified according to AMD stages. Eyes with GA were divided into two groups regarding foveal involvement. Baseline factors were compared between eyes with foveal GA (FGA) and eyes with non-foveal GA (NFGA) to identify predictive factors for foveal involvement. Results: A total of 2033 eyes from 1027 patients were included. AMD stage was early in 296 (14.5%) cases, intermediate in 368 (18.1%) cases, and advanced in 1249 (61.4%) cases. A total of 1204 (60%) eyes had GA [932 (77%) FGA and 272 (23%) NFGA], while 125 eyes (27.4% from eyes with advanced dry AMD) met the indication criteria for treatment with intravitreal pegcetacoplan. The proportion of eyes with neovascular AMD was significantly higher in the FGA group compared to the NFGA group [598 (64.2%) vs. 152 (55.8%), p = 0.01]. Conclusions: At least a quarter of eyes with advanced AMD would be suitable for the upcoming intravitreal pegcetacoplan therapy. Foveal involvement of GA in advanced AMD seems to be more likely in neovascular AMD than in dry AMD.
Urethra-Sparing Robot-Assisted Simple Prostatectomy for Postoperative Antegrade Ejaculation
Authors: Choi Sae Woong , Sohn Dong Wan , Ha U-Syn , Hong Sung-Hoo , Lee Ji Youl , Cho Hyuk Jin
Published: July 2023

Background: We report a comparative analysis of extraperitoneal urethra-sparing robot-assisted simple prostatectomy (EUS-RASP) versus robot-assisted simple prostatectomy (RASP) using the Freyer approach for patients with a large prostate volume greater than 80 mL. Methods: A total of 32 patients underwent EUS-RASP, and 30 underwent RASP from April 2018 to November 2021. All the perioperative data and 6-month follow-up data were collected prospectively. We retrospectively evaluated baseline characteristics and functional outcomes, including International Prostate Symptom Scores (IPSSs) and quality of life (QOL), maximum flow rate, and post-void residual volume, between the two groups. Sexual function was analyzed in the EUS-RASP group. Results: The patients undergoing EUS-RASP and RASP had comparable baseline characteristics and functional outcomes. The EUS-RASP group showed a shorter operative time (123.4 ± 15.2 min vs. 133.7 ± 21.4 min, p = 0.034), length of hospital stay (2.9 ± 1.5 days vs. 4.6 ± 1.5 days, p = 0.001), and catheterization time (2.4 ± 1.7 days vs. 8.1 ± 2.4 days, p < 0.001). A total of 14/32 (43.8%) patients reported normal preoperative ejaculatory function in the EUS-RASP group, and 11/14 (78.6%) maintained antegrade ejaculation postoperatively. Conclusions: Extraperitoneal urethra-sparing RASP is an effective and feasible procedure that can improve voiding function and allow for the maintenance of ejaculatory function in patients with large prostates.
Intravitreal Aflibercept for Patients with Acute Nonarteritic Anterior Ischemic Optic Neuropathy: A Retrospective Trial
Authors: Cheng Kai-Chun , Chiu Chien-Chih , Chen Kuo-Jen , Chang Yo-Chen
Published: July 2023

Purpose: This study aimed to investigate whether intravitreal aflibercept was safe and effective in patients with acute nonarteritic anterior ischemic optic neuropathy (NAION). Methods: This was a chart study of 25 individuals with acute NAION (25 eyes). An intravitreal injection of 2 mg/0.05 mL of aflibercept was administered to fifteen participants. The remaining ten patients in the control group were given standard care. The researchers measured the initial visual acuity, retinal nerve fiber layer thickness (RNFLT), and automated perimetry. During the follow-up period, the researchers measured the final visual acuity, RNFLT, automated perimetry, and side effects. Results: Visual acuity and visual field assessment were significantly improved in the study group, and optical coherence tomography testing demonstrated significant disc edema resolution. The therapy results differed significantly between the two groups regarding visual outcomes (F = 0.027, p = 0.039) and RNFLT decrease (F = 5.507, p = 0.003). However, the difference in visual field alterations was not significant (F = 0.724, p = 0.387). Conclusions: Intravitreal injection of aflibercept can significantly improve visual acuity and resolve disc edema in patients with acute NAION. Intravitreal aflibercept may be an alternative treatment for acute NAION. However, a large series investigation is needed to assess the long-term therapeutic benefit and safety of intravitreal aflibercept in patients with acute NAION.
Effect of Cardiovascular Risk Factors on 30-Day All-Cause Mortality in Cardiogenic Shock
Authors: Forner Jan , Schupp Tobias , Weidner Kathrin , Ruka Marinela , Egner-Walter Sascha , Behnes Michael , Akin Muharrem , Ayoub Mohamed , Mashayekhi Kambis , Akin Ibrahim , Rusnak Jonas
Published: July 2023

Although previous studies investigated the influence of cardiovascular risk (CVR) factors in patients with acute coronary syndrome, data concerning the effect of CVR factors on the prognosis of patients with cardiogenic shock (CS) is scarce. Consecutive patients with CS were prospectively included from 2019 to 2021. The prognosis of patients with “low CVR” (i.e., 0–1 CVR factors) was compared to patients with “high CVR” (i.e., 2–4 CVR factors) according to presence or absence of arterial hypertension, diabetes mellitus, hyperlipidaemia or smoking. The primary endpoint was 30-day all-cause mortality. Statistical analyses included Kaplan-Meier and Cox proportional regression analyses. 273 consecutive patients with CS were included. 28% presented with low CVR and 72% with high CVR. Within the entire study cohort, the risk of 30-day all-cause mortality did not differ between patients with high and low CVR (55% vs. 57%; log rank p = 0.727; HR = 0.942; 95% CI 0.663–1.338; p = 0.738). Even after multivariable adjustment, high CVR was not associated with an elevated risk of 30-day all-cause mortality (HR = 1.039; 95% CI 0.648–1.667; p = 0.873). The presence of arterial hypertension (55% vs. 58%; log rank p = 0.564; HR = 0.906; 95% CI 0.638–1.287; p = 0.582), diabetes mellitus (60% vs. 52%; log rank p = 0.215; HR = 1.213; 95% CI 0.881–1.671; p = 0.237) and a history of smoking (56% vs. 56%; log rank p = 0.725; HR = 0.945; 95% CI 0.679–1.315; p = 0.737) did not significantly influence short-term prognosis.. Only the absence of hyperlipidaemia significantly decreased the risk of all-cause mortality (65% vs. 51%; log rank p = 0.038; HR = 0.718; 95% CI 0.516–0.998; p = 0.049), which was no longer observed after multivariable adjustment (HR = 0.801; 95% CI 0.536–1.195; p = 0.277). In conclusion, neither the overall CVR nor individual CVR factors were associated with the risk of 30-day all-cause mortality in patients with CS.
Anticytokine Autoantibodies and Fungal Infections
Authors: Kappagoda Shanthi , Deresinski Stanley
Published: July 2023

Anticytokine autoantibodies (ACAAs) can cause adult onset immunodeficiencies which mimic primary immunodeficiencies and can present as refractory and severe fungal infections. This paper provides an overview of the role of innate immunity, including key cytokines, in fungal infections and then describes four clinical scenarios where ACAAs are associated with severe presentations of a fungal infection: (1) Talaromyces marneffei infection and anti-interferon-γ, (2) histoplasmosis and anti-interferon-γ, (3) Cryptococcus gattii infection and anti-GM-CSF, and (4) mucocutaneous candidiasis and anti-IL-17A/F (IL-22). Testing for ACAAs and potential therapeutic options are discussed.
Influence of the Bile Acid Transporter Genes ABCB4, ABCB8, and ABCB11 and the Farnesoid X Receptor on the Response to Ursodeoxycholic Acid in Patients with Nonalcoholic Steatohepatitis
Authors: Kreimeyer Henriette , Vogt Katharina , Götze Tobias , Best Jan , Götze Oliver , Weigt Jochen , Kahraman Alisan , Özçürümez Mustafa , Kälsch Julia , Syn Wing-Kin , Sydor Svenja , Canbay Ali , Manka Paul
Published: July 2023

The prevalence of NAFLD and NASH is increasing worldwide, and there is no approved medical treatment until now. Evidence has emerged that interfering with bile acid metabolism may lead to improvement in NASH. In this study, 28 patients with elevated cholestatic liver function tests (especially GGT) were screened for bile acid gene polymorphisms and treated with UDCA. All patients had a bile acid gene polymorphism in ABCB4 or ABCB11. Treatment with UDCA for 12 months significantly reduced GGT in all patients and ALT in homozygous patients. No difference in fibrosis was observed using FIb-4, NFS, and transient elastography (TE). PNPLA3 and TM6SF2 were the most common NASH-associated polymorphisms, and patients with TM6SF2 showed a significant reduction in GGT and ALT with the administration of UDCA. In conclusion, NASH patients with elevated GGT should be screened for bile acid gene polymorphisms, as UDCA therapy may improve liver function tests. However, no difference in clinical outcomes, such as progression to cirrhosis, has been observed using non-invasive tests (NITs).
Exploration of Spatio-Temporal Evolution and Threshold Effect of Shrinking Cities
Authors: Song Yuanzhen , He Weijie , Zeng Jian
Published: July 2023

Shrinking cities are a global issue with regional characteristics. This paper focuses on the county-level administrative units in the Three Northeastern Provinces in China to identify and classify shrinking cities using a two-step identification method and explores their spatial-temporal evolution. The paper utilizes the panel threshold regression model for empirical testing. The results indicate the following: (1) The number of shrinking cities in the region is large and deep. Quantitatively, the shrinking cities account for about 50% of the whole; spatially, there are six major shrinking city “groups”, showing the distribution trend around the “Ha-Da” urban corridor. (2) The threshold effect test reveals that GDP is a critical threshold variable influencing the formation of shrinking cities. Moreover, cities are classified into three types based on the threshold values: Type I (GDP > 2,270,731 yuan), Type II (434,832 < GDP ≤ 2,270,731), and Type III (GDP < 434,832). (3) The results of the dual-threshold and grouped regression models show significant variations in the dominant factors of shrinking cities of different scales. Variables such as impervious area, fiscal revenue, and grass area demonstrate relatively stable promoting effects.
Neural Rendering-Based 3D Scene Style Transfer Method via Semantic Understanding Using a Single Style Image
Authors: Park Jisun , Cho Kyungeun
Published: July 2023

In the rapidly emerging era of untact (“contact-free”) technologies, the requirement for three-dimensional (3D) virtual environments utilized in virtual reality (VR)/augmented reality (AR) and the metaverse has seen significant growth, owing to their extensive application across various domains. Current research focuses on the automatic transfer of the style of rendering images within a 3D virtual environment using artificial intelligence, which aims to minimize human intervention. However, the prevalent studies on rendering-based 3D environment-style transfers have certain inherent limitations. First, the training of a style transfer network dedicated to 3D virtual environments demands considerable style image data. These data must align with viewpoints that closely resemble those of the virtual environment. Second, there was noticeable inconsistency within the 3D structures. Predominant studies often neglect 3D scene geometry information instead of relying solely on 2D input image features. Finally, style adaptation fails to accommodate the unique characteristics inherent in each object. To address these issues, we propose a novel approach: a neural rendering-based 3D scene-style conversion technique. This methodology employs semantic nearest-neighbor feature matching, thereby facilitating the transfer of style within a 3D scene while considering the distinctive characteristics of each object, even when employing a single style image. The neural radiance field enables the network to comprehend the geometric information of a 3D scene in relation to its viewpoint. Subsequently, it transfers style features by employing the unique features of a single style image via semantic nearest-neighbor feature matching. In an empirical context, our proposed semantic 3D scene style transfer method was applied to 3D scene style transfers for both interior and exterior environments. This application utilizes the replica, 3DFront, and Tanks and Temples datasets for testing. The results illustrate that the proposed methodology surpasses existing style transfer techniques in terms of maintaining 3D viewpoint consistency, style uniformity, and semantic coherence.
Optimum Route and Transport Mode Selection of Multimodal Transport with Time Window under Uncertain Conditions
Authors: Li Lin , Zhang Qiangwei , Zhang Tie , Zou Yanbiao , Zhao Xing
Published: July 2023

Aiming at the problem of multimodal transport path planning under uncertain environments, this paper establishes a multi-objective fuzzy nonlinear programming model considering mixed-time window constraints by taking cost, time, and carbon emission as optimization objectives. To solve the model, the model is de-fuzzified by the fuzzy expectation value method and fuzzy chance-constrained planning method. Combining the game theory method with the weighted sum method, a cooperative game theory-based multi-objective optimization method is proposed. Finally, the effectiveness of the algorithm is verified in a real intermodal network. The experimental results show that the proposed method can effectively improve the performance of the weighted sum method and obtain the optimal multimodal transport path that satisfies the time window requirement, and the path optimization results are better than MOPSO and NSGA-II, effectively reducing transportation costs and carbon emissions. Meanwhile, the influence of uncertainty factors on the multimodal transport route planning results is analyzed. The results show that the uncertain factors will significantly increase the transportation cost and carbon emissions and affect the choice of route and transportation mode. Considering uncertainty factors can increase the reliability of route planning results and provide a more robust and effective solution for multimodal transportation.
A Review on Membrane Fouling Prediction Using Artificial Neural Networks (ANNs)
Authors: Abuwatfa Waad H. , AlSawaftah Nour , Darwish Naif , Pitt William G. , Husseini Ghaleb A.
Published: July 2023

Membrane fouling is a major hurdle to effective pressure-driven membrane processes, such as microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO). Fouling refers to the accumulation of particles, organic and inorganic matter, and microbial cells on the membrane’s external and internal surface, which reduces the permeate flux and increases the needed transmembrane pressure. Various factors affect membrane fouling, including feed water quality, membrane characteristics, operating conditions, and cleaning protocols. Several models have been developed to predict membrane fouling in pressure-driven processes. These models can be divided into traditional empirical, mechanistic, and artificial intelligence (AI)-based models. Artificial neural networks (ANNs) are powerful tools for nonlinear mapping and prediction, and they can capture complex relationships between input and output variables. In membrane fouling prediction, ANNs can be trained using historical data to predict the fouling rate or other fouling-related parameters based on the process parameters. This review addresses the pertinent literature about using ANNs for membrane fouling prediction. Specifically, complementing other existing reviews that focus on mathematical models or broad AI-based simulations, the present review focuses on the use of AI-based fouling prediction models, namely, artificial neural networks (ANNs) and their derivatives, to provide deeper insights into the strengths, weaknesses, potential, and areas of improvement associated with such models for membrane fouling prediction.
Growth Response of Non-Conventional Yeasts on Sugar-Rich Media: Part 1: High Production of Lipid by Lipomyces starkeyi and Citric Acid by Yarrowia lipolytica
Authors: Diamantopoulou Panagiota , Sarris Dimitris , Tchakouteu Sidoine Sadjeu , Xenopoulos Evangelos , Papanikolaou Seraphim
Published: July 2023

Sugar-rich waste streams, generated in very high quantities worldwide, constitute an important source of environmental pollution. Their eco-friendly conversions into a plethora of added-value compounds through the use of microbial fermentations is currently a very “hot” scientific topic. The aim of this study, was to assess the potential of single cell oil (SCO), microbial mass and citric acid (CA) production by non-conventional yeast strains growing on expired (“waste”) glucose. Six yeast strains (viz. Rhodosporidium toruloides DSM 4444, Rhodotorula glutinis NRRL YB-252, R. toruloides NRRL Y-27012, Yarrowia lipolytica LFMB Y-20, Y. lipolytica ACA-DC 50109 and Lipomyces starkeyi DSM 70296) were initially grown in shake flasks with expired glucose used as substrate under nitrogen limitation, in order to “boost” the cellular metabolism towards the synthesis of SCO and CA, and their growth response was quantitatively evaluated. Initial glucose concentration (Glc0) was adjusted at c. 50 g/L. Besides Y. lipolytica, all other yeast strains produced noticeable SCO quantities [lipid in dry cell weight (DCW) ranging from 25.3% w/w to 55.1% w/w]. Lipids of all yeasts contained significant quantities of oleic acid, being perfect candidates for the synthesis of 2nd generation biodiesel. The highest DCW production (=13.6 g/L) was obtained by L. starkeyi DSM 70296, while both Y. lipolytica strains did not accumulate noticeable lipid quantities, but produced non-negligible CA amounts. The most promising CA-producing strain, namely Y. lipolytica ACA-DC 50109 was further studied in stirred-tank bioreactor systems, while the very promising DCW- and SCO-producing L. starkeyi DSM 70296 was further studied in shake flasks. Both strains were grown on media presenting higher Glc0 concentrations and the same initial nitrogen quantity as previously. Indeed, L. starkeyi grown at Glc0 = 85 g/L, produced DCWmax = 34.0 g/L, that contained lipid =34.1% w/w (thus SCO was =11.6 g/L). The strain ACA-DC 50109 in stirred tank bioreactor with Glc0 ≈ 105 g/L produced CA up to 46 g/L (yield of CA produced on glucose consumed; YCA/Glc ≈ 0.45 g/g). Finally, in fed-batch bioreactor experiment, the significant CA quantity of 82.0 g/L (YCA/Glc = 0.50 g/g) was recorded. Concluding, “waste” glucose proved to be a suitable substrate for a number of non-conventional yeast strains. Y. lipolytica ACA-DC 50109 produced significant quantities of CA while L. starkeyi DSM 70296 was a very interesting DCW- and SCO-producing candidate. These strains can be used as potential cell factories amenable to convert glucose-based residues into the mentioned metabolic compounds, that present high importance for food, chemical and biofuel facilities.
Rhizobacteria Increase the Adaptation Potential of Potato Microclones under Aeroponic Conditions
Authors: Tkachenko Oksana V. , Evseeva Nina V. , Kargapolova Kristina Y. , Denisova Alena Y. , Pozdnyakova Natalia N. , Kulikov Artem A. , Burygin Gennady L.
Published: July 2023

Adaptation ex vitro is strongly stressful for microplants. Plant-growth-promoting rhizobacteria (PGPR) help to increase the adaptation potential of microplants transplanted from test tubes into the natural environment. We investigated the mechanisms of antioxidant protection of PGPR-inoculated potato microclones adapting to ex vitro growth in an aeroponic system. Potato (Solanum tuberosum L. cv. Nevsky) microplants were inoculated in vitro with the bacteria Azospirillum baldaniorum Sp245 and Ochrobactrum cytisi IPA7.2. On days 1 and 7 of plant growth ex vitro, catalase and peroxidase activities in the leaves of inoculated plants were 1.5-fold higher than they were in non-inoculated plants. The activity of ascorbate peroxidase was reduced in both in vitro and ex vitro treatments, and this reduction was accompanied by a decrease in the leaf content of hydrogen peroxide and malondialdehyde. As a result, inoculation contributed to the regulation of the plant pro/antioxidant system, lowering the oxidative stress and leading to better plant survival ex vitro. This was evidenced by the higher values of measured morphological and physiological variables of the inoculated plants, as compared with the values in the control treatment. Thus, we have shown some PGPR-mediated mechanisms of potato plant protection from adverse environmental factors under aeroponic conditions.
A New Anisotropic Singularity Algorithm to Characterize Geo-Chemical Anomalies in the Duolong Mineral District, Tibet, China
Authors: Tang Jie , Wang Wenlei , Yuan Changjiang
Published: July 2023

With the increasing exploitation of mineral resources by humans, exploring non-traditional areas for hidden resources such as deep earth and sediment-covered regions has become a significant challenge in the field of mineral exploration. Geochemical data, as a crucial information carrier of geological bodies, serves as one of the direct and effective sources for quantitative analysis of regional geological evolution and mineralization prediction studies. It plays an indispensable role in geographic information system (GIS)-based mineral exploration. Due to the neglect of spatial distribution characteristics and the variability of statistical features with spatial metrics in traditional statistical methods, this paper employs fractal/multifractal and the local singularity analysis to identify geochemical anomalies from background and characterize geochemical distributions associated with porphyry Cu-Au mineralization in the Duolong mineral district, Tibet, China. A novel algorithm for estimating the singularity index, which takes anisotropy into consideration, is proposed and practically applied to the Duolong district. By comparing with the isotropic singularity index, this new method objectively identifies anisotropic geochemical signatures and investigates non-linear behaviors of ore-forming elements, making it more practical and effective in geo-anomaly extraction. Furthermore, the current method is capable of indicating variations in geochemical distributions at different scales through directional arrows marking analytical windows. The summed-up direction of these multi-scale vectors effectively demonstrates migration trends of ore materials at each location within the study area. The new method can pinpoint the location of ore-forming element accumulation and migration directions, unlocking valuable insights from complex datasets. This promises to revolutionize our understanding of how minerals are formed and distributed within the Earth’s crust.
Recent Advances in Fluorescent Nanoprobes for Food Safety Detection
Authors: Yuan Huanxiang , Li Yutong , Lv Jiaqi , An Yunhe , Guan Di , Liu Jia , Tu Chenxiao , Wang Xiaoyu , Zhou Huijuan
Published: July 2023

Fluorescent nanoprobes show similar fluorescence properties to traditional organic dyes, but the addition of nanotechnology accurately controls the size, shape, chemical composition, and surface chemistry of the nanoprobes with unique characteristics and properties, such as bright luminescence, high photostability, and strong biocompatibility. For example, modifying aptamers or antibodies on a fluorescent nanoprobe provides high selectivity and specificity for different objects to be tested. Fluorescence intensity, life, and other parameters of targets can be changed by different sensing mechanisms based on the unique structural and optical characteristics of fluorescent nanoprobes. What’s more, the detection of fluorescent nanoprobes is cost-saving, simple, and offers great advantages in rapid food detection. Sensing mechanisms of fluorescent nanoprobes were introduced in this paper, focusing on the application progress in pesticide residues, veterinary drug residues, heavy metals, microbes, mycotoxins, and other substances in food safety detection in recent years. A brief outlook for future development was provided as well.
Phosphoproteome Profiling of uEVs Reveals p-AQP2 and p-GSK3β as Potential Markers for Diabetic Nephropathy
Authors: Li Qing , Zhang Jiong , Fang Yi , Dai Yan , Jia Ping , Shen Ziyan , Xu Sujuan , Ding Xiaoqiang , Zhou Feng
Published: July 2023

Diabetic nephropathy (DN) contributes to increased morbidity and mortality among patients with diabetes and presents a considerable global health challenge. However, reliable biomarkers of DN have not yet been established. Phosphorylated proteins are crucial for disease progression. However, their diagnostic potential remains unexplored. In this study, we used ultra-high-sensitivity quantitative phosphoproteomics to identify phosphoproteins in urinary extracellular vesicles (uEVs) as potential biomarkers of DN. We detected 233 phosphopeptides within the uEVs, with 47 phosphoproteins exhibiting significant alterations in patients with DN compared to those in patients with diabetes. From these phosphoproteins, we selected phosphorylated aquaporin-2 (p-AQP2[S256]) and phosphorylated glycogen synthase kinase-3β (p-GSK3β[Y216]) for validation, as they were significantly overrepresented in pathway analyses and previously implicated in DN pathogenesis. Both phosphoproteins were successfully confirmed through Phos-tag western blotting in uEVs and immunohistochemistry staining in kidney sections, suggesting that phosphoprotein alterations in uEVs reflect corresponding changes within the kidney and their potential as candidate biomarkers for DN. Our research proposes the utilization of phosphoproteins in uEVs as a liquid biopsy, presenting a highly feasible diagnostic tool for kidney disease.
Application of Cyclodextrin for Cancer Immunotherapy
Authors: Wei Xiaojie , Yu Cui-Yun , Wei Hua
Published: July 2023

Tumor immunotherapy, compared with other treatment strategies, has the notable advantage of a long-term therapeutic effect for preventing metastasis and the recurrence of tumors, thus holding great potential for the future of advanced tumor therapy. However, due to the poor water solubility of immune modulators and immune escape properties of tumor cells, the treatment efficiency of immunotherapy is usually significantly reduced. Cyclodextrin (CD) has been repeatedly highlighted to be probably one of the most investigated building units for cancer therapy due to its elegant integration of an internal hydrophobic hollow cavity and an external hydrophilic outer surface. The application of CD for immunotherapy provides new opportunities for overcoming the aforementioned obstacles. However, there are few published reviews, to our knowledge, summarizing the use of CD for cancer immunotherapy. For this purpose, this paper provides a comprehensive summary on the application of CD for immunotherapy with an emphasis on the role, function, and reported strategies of CD in mediating immunotherapy. This review summarizes the research progress made in using CD for tumor immunotherapy, which will facilitate the generation of various CD-based immunotherapeutic delivery systems with superior anticancer efficacy.
NiCo-MOF Nanospheres Created by the Ultra-Fast Microwave Method for Use in High-Performance Supercapacitors
Authors: Yang Xing , Zhang Xin , Yang Ning , Yang Lei , Wang Wanglong , Fang Xing , He Qing
Published: July 2023

Metal-organic frameworks—through the use of creative synthetic designs—could produce MOF materials with excellent porosity, stability, particle microstructures, and conductivity, and their inherent characteristics—including their porosity and controllable structure—may result in an immense number of prospects for energy storage. In this paper, a nanosphere-like NiCo-MOF was effectively manufactured via an ultra-fast microwave technique. Additionally, the ideal synthesis conditions of the NiCo-MOF were investigated by adjusting the microwave output power and microwave reaction time. Under the reaction conditions of a 600 W microwave and a 210 s microwave reaction time, the NiCo-MOF exhibited an excellent capacitance of 1348 F/g at a current density of 1 A/g and an 86.1% capacity retention rate at 10 A/g. In addition, self-assembled NiCo-MOF/AC asymmetric capacitors showed a splendid energy density of 46.6 Wh/kg and a power density of 8000 W/kg.
Preparation of NH4Cl-Modified Carbon Materials via High-Temperature Calcination and Their Application in the Negative Electrode of Lead-Carbon Batteries
Authors: Zhang Meng , Song Hengshuai , Ma Yujia , Yang Shaohua , Xie Fazhi
Published: July 2023

The performance of lead-acid batteries could be significantly increased by incorporating carbon materials into the negative electrodes. In this study, a modified carbon material developed via a simple high-temperature calcination method was employed as a negative electrode additive, and we have named it as follows: N-doped chitosan-derived carbon (NCC). The performance of this material was compared with a control battery containing activated carbon (AC). X-ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy were engaged in analyzing the crystal structure and morphology of the material. Afterwards, the electrochemical and battery performance was examined through cyclic voltammetry (CV), linear voltammetry (LSV) and constant current charge-discharge testing. Markedly, the electrode plate containing 1 wt.% NCC indicates the highest specific capacity (106.48 F g−1) as compared to the control battery, which is 1.56 times higher than the AC electrode plate and 4.75 times higher than the blank electrode plate. The linear voltammetry shows that the hydrogen precipitation current density of the 1 wt.% NCC electrode plate is only −0.028 A cm−2, a much higher value than that of the AC electrode plate. In addition, the simulated battery containing 1 wt.% NCC has a cycle life of 4324 cycles, which is 2.36 times longer than that of the same amount of additive AC battery (1834 cycles) and 5.34 times longer than that of the blank battery (809 cycles). In summary, NCC carbon has the advantage of extending the life of lead-acid batteries, rendering it a promising candidate for lead-acid battery additives.