bluuebunny/crossref_metadata_2025 huggingface dataset:
Retain or remove? Decision-making of rural industrial park redevelopment in Nanhai District, China
Authors: Liu Zhuojun , Fang Hongjia , Xu Shanshan , Wu Yilin , Wen Keyin , Shen Zitong , Wang Hongmei
Published: February 2024

Introduction: In both of China and other industrializing countries, improving the efficiency of degraded industrial land use will help control urban sprawl brought about by rapid urbanization. The redevelopment of industrial parks in the countryside is becoming a starting point for phasing out high-polluting industries and an important source of land supply for high-end and green industries. The objective of this paper is to identify how the local state of China determines the necessity for the demolition of rural industrial parks (RIPs) and how this process reflects the underlying decision-making mechanisms.

Methodology: This paper carries out descriptive spatial analysis by combining the economic and social development cross-sectional data in 2019 and extracts data from the Baidu Map to calculate the traffic network density. Cluster analysis is also used to group the RIPs according to their data characteristics. In order to provide an in-depth discussion of the cases, the authors also overlay the results of the spatial and cluster analyses.

Results: The spatial distribution of RIPs is closely related to their location and transportation conditions. Failure of the market has resulted in large tracts of advantageous land being taken up by inefficient industrial parks. Cluster analysis and overlay analysis have evaluated the difficulty of redevelopment and divided the industrial parks into three clusters: retained RIPs, medium-term removed RIPs, and near-term-removed RIPs. The authors put forward that different strategies should be adopted for the future renovation of medium-term-removed and near-term-removed RIPs.

Discussion: This paper argues that proper categorization is the beginning of feasible RIP redevelopment. Local governments should resist the temptation of short-term land transfer revenues to achieve long-term growth. The significant differences in concerns between the grassroots and the higher levels of government also require that the effects of bottom-up influence and top-down intervention should be balanced.
Putative molecular markers of Plasmodium falciparum resistance to antimalarial drugs in malaria parasites from Ghana
Authors: Matrevi Sena Adzoa , Adams Tryphena , Tandoh Kwesi Zandoh , Opoku-Agyeman Philip , Bruku Selassie , Ennuson Nana Aba , Apau-Danso Paa Kwesi , Fiagbedzi Emmanuel , Avornyo Mary , Myers Charles James , Futagbi Joy , Hagan Oheneba Charles , Abuaku Benjamin , Koram Kwadwo Ansah , Awandare Gordon , Quashie Neils Ben , Duah-Quashie Nancy Odurowah
Published: February 2024

Introduction

Antimalarial drugs including artemisinin-based combination therapy (ACT) regimens and sulphadoxine-pyrimethamine (SP) are used in Ghana for malaria therapeutics and prophylaxis respectively. The genetic basis of Plasmodium falciparum development of drug resistance involves single nucleotide polymorphisms in genes encoding proteins for multiple cellular and metabolic processes. The prevalence of single nucleotide polymorphisms in nine P. falciparum genes linked to ACT and SP resistance in the malaria parasite population was determined.

Methods

Archived filter paper blood blot samples from patients aged 9 years and below with uncomplicated malaria reporting at 10 sentinel sites located in three ecological zones for the Malaria Therapeutic Efficacy Studies were used. The samples used were collected from 2007-2018 malaria transmission seasons and mutations in the genes were detected using PCR and Sanger sequencing.

Results

In all 1,142 samples were used for the study. For falcipain-2 gene (pffp2), Sanger sequencing was successful for 872 samples and were further analysed. The prevalence of the mutants was 45% (392/872) with pffp2 markers V51I and S59F occurring in 15.0% (128/872) and 3.0% (26/872) of the samples respectively. Prevalence of other P. falciparum gene mutations: coronin (pfcoronin) was 44.8% (37/90); cysteine desulfurase (pfnfs) was 73.9% (68/92); apicoplast ribosomal protein S10 (pfarps10) was 36.8% (35/95); ferredoxin (pffd) was 8.8% (8/91); multidrug resistance protein-1 (pfmrp1) was 95.2.0% (80/84); multidrug resistance protein-2 (pfmrp2) was 91.4% (32/35); dihydrofolate reductase (pfdhfr) was 99.0% (84/85); dihydropteroate synthase (pfdhps) was 72% (68/95).

Discussion

The observation of numerous mutations in these genes of interest in the Ghanaian isolates, some of which have been implicated in delayed parasite clearance is of great interest. The presence of these genotypes may account for the decline in the efficacies of ACT regimens being used to treat uncomplicated malaria in the country. The need for continuous monitoring of these genetic markers to give first-hand information on parasite susceptibility to antimalarial drugs to inform policy makers and stakeholders in malaria elimination in the country is further discussed.
Salinity-mediated limitation of asexual reproduction in the colonial ascidian Polyandrocarpa zorritensis
Authors: Tobias-Santos Vitoria , Andreoni-Pham Rita , El Gharbi Dany , Lebel Marie , Tiozzo Stefano , Alié Alexandre
Published: February 2024

Ascidians are among the most common invasive marine invertebrates worldwide. Many species of non-indigenous ascidians (NIAs) have successfully colonized the Mediterranean Sea, notably within anthropized coastal lagoons and harbors. Although invasive species are generally characterized by their broad ecological tolerance, different ascidian species exhibit varied responses to biotic and abiotic environmental stressors, including temperature and salinity. Acquiring a better understanding about of the impact of such parameters on ascidian life history is crucial for predicting the invasive potential of NIAs. In this study, we investigated the impact of various salinities on the reproduction of the colonial ascidian Polyandorcarpa zorritensis, a species indigenous to Peru and a thriving invader. P. zorritensis undergoes asexual reproduction via a peculiar form of budding named vasal budding and produces resistant spherules, which likely facilitated its dissemination over long distances. Despite its widespread distribution along the Pacific and Atlantic coasts, it is only found in a few Mediterranean coastal areas with a low salinity. We tested the impact of different salinity conditions on the sexual and asexual reproduction rates of P. zorritensis in a controlled laboratory setting. Our experiments showed that the rate of asexual reproduction in colonies bred at 29 or 36 ppt salinity levels, corresponding to the natural range inhabited by P. zorritensis, was higher than those grown in 40 ppt salinity, commonly found in Mediterranean marinas and harbors. The results suggest that, although P. zorritensis has been present in the Mediterranean for several decades, its potential for invasion could be constrained by an intolerance to high salinity.
Non-perennial rivers and streams in extreme hydrological conditions—comparing the effectiveness of amplicon sequencing and digital microscopy for diatom biodiversity appraisal
Authors: Burfeid-Castellanos Andrea M. , Mones Phillip , Dani Mimoza , Beszteri Bánk
Published: February 2024

Introduction

Non-perennial rivers and streams are increasingly present, in part because of climate change, even in the temperate climate. However, how the loss of connectivity and complete drying affect microphytobenthos in general and diatom communities in particular has gone mostly unstudied.

Methods

With this paper, we aim to close this gap, identifying diatom biodiversity through manual digital microscopy and rbcL amplicon sequencing, to observe a) which method is better suited to it and b) how the ecotone flow-pool-dry affects diatom diversity under duress. Three karstic, non-perennial rivers and streams with a gradient from natural to anthropogenically disturbed were sampled under flooding conditions and after a long and intense drought in 2022.

Results

Our results show that digital microscopy shows a higher diversity and species richness than amplicon sequencing. We posit that this might be due to a reduced pool of subaerophile taxa having been sequenced and being part of the reference database. Furthermore, the effect of drying only resulted in a reduction in diversity after this drought, although the biofilm was still alive under these conditions.

Discussion

To use amplicon sequencing for non-perennial river diatom diversity monitoring, the reference databases will have to be adapted to such systems, as most rivers may be subjected to drying regularly in the future.
Multi-omics analysis of miRNA-mediated intestinal microflora changes in crucian carp Carassius auratus infected with Rahnella aquatilis
Authors: Huo Jiaxin , Li Xiaowei , Hu Xiucai , Lv Aijun
Published: February 2024

Infection by an emerging bacterial pathogen Rahnella aquatilis caused enteritis and septicemia in fish. However, the molecular pathogenesis of enteritis induced by R. aquatilis infection and its interacting mechanism of the intestinal microflora associated with microRNA (miRNA) immune regulation in crucian carp Carassius auratus are still unclear. In this study, C. auratus intraperitoneally injected with R. aquatilis KCL-5 was used as an experimental animal model, and the intestinal pathological changes, microflora, and differentially expressed miRNAs (DEMs) were investigated by multi-omics analysis. The significant changes in histopathological features, apoptotic cells, and enzyme activities (e.g., lysozyme (LYS), alkaline phosphatase (AKP), alanine aminotransferase (ALT), aspartate transaminase (AST), and glutathione peroxidase (GSH-Px)) in the intestine were examined after infection. Diversity and composition analysis of the intestinal microflora clearly demonstrated four dominant bacteria: Proteobacteria, Fusobacteria, Bacteroidetes, and Firmicutes. A total of 87 DEMs were significantly screened, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the potential target genes were mainly involved in the regulation of lipid, glutathione, cytosine, and purine metabolism, which participated in the local immune response through the intestinal immune network for IgA production, lysosome, and Toll-like receptor (TLR) pathways. Moreover, the expression levels of 11 target genes (e.g., TLR3, MyD88, NF-κB, TGF-β, TNF-α, MHC II, IL-22, LysC, F2, F5, and C3) related to inflammation and immunity were verified by qRT-PCR detection. The correlation analysis indicated that the abundance of intestinal Firmicutes and Proteobacteria was significantly associated with the high local expression of miR-203/NF-κB, miR-129/TNF-α, and miR-205/TGF-β. These findings will help to elucidate the molecular regulation mechanism of the intestinal microflora, inflammation, and immune response-mediated miRNA–target gene axis in cyprinid fish.
Complete Freund’s adjuvant as a confounding factor in multiple sclerosis research
Authors: Lazarević Milica , Stanisavljević Suzana , Nikolovski Neda , Dimitrijević Mirjana , Miljković Đorđe
Published: February 2024

Complete Freund’s adjuvant (CFA) is used as a standard adjuvant for the induction of experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model in multiple sclerosis studies. Still, CFA induces glial activation and neuroinflammation on its own and provokes pain. In addition, as CFA contains Mycobacteria, an immune response against bacterial antigens is induced in parallel to the response against central nervous system antigens. Thus, CFA can be considered as a confounding factor in multiple sclerosis–related studies performed on EAE. Here, we discuss the effects of CFA in EAE in detail and present EAE variants induced in experimental animals without the use of CFA. We put forward CFA-free EAE variants as valuable tools for studying multiple sclerosis pathogenesis and therapeutic approaches.
Sponges on shifting reefs: holobionts show similar molecular and physiological responses to coral versus macroalgal food
Authors: Campana Sara , Arts Milou G. I. , Díez-Vives Cristina , Mueller Benjamin , Bang Corinna , Riesgo Ana , Haas Andreas F. , Muyzer Gerard , de Goeij Jasper M.
Published: February 2024

Introduction

Many coral reefs witness an ongoing coral-to-algae phase shift. Corals and algae release large quantities of (in)organic nutrients daily, of which a large part is utilized by sponges. In turn, sponges are important cyclers of precious resources to other inhabitants on reefs residing in oligotrophic waters. Here, we investigated whether sponge holobionts (i.e., host and prokaryotic symbionts) adapt their physiology to food released by coral- versus macroalgae.

Methods

Thereto, two sponge species, Plakortis angulospiculatus and Halisarca caerulea (high and low microbial abundance, respectively), were continuously exposed for 12 days to coral and macroalgal exudates in running seawater aquaria. Transcript expression of host and prokaryotic symbionts, changes in prokaryotic community composition, and holobiont physiological responses (i.e., respiratory demand, fluxes of carbon and nitrogen) were investigated after coral- versus macroalgae dominated treatments and compared to a seawater only control treatment.

Results

In both sponge holobionts differential transcript expression between the coral and macroalgae treatments was very low (<0.01% of total transcripts). Differential expression was found in genes targeting cellular signaling pathways, e.g., cell proliferation (upregulated in coral treatment), and immune response (upregulated in macroalgal treatment). The sponge-associated prokaryotic community composition and sponge physiological responses were similar in all treatments, yet differed significantly between the two species.

Discussion

After 12 days of exposure sponges appear to opportunistically feed on different food sources without having to adjust their metabolic pathways or associated prokaryotic communities. This suggests that sponges could be well-adapted to predicted changes in food source availability due to coral-to-algal phase shifts on many coral reefs.
Plant growth regulators improve the growth and physiology of transplanted Thalassia Hemprichii fragments
Authors: Li Zhaoyang , Shi Yunfeng , Zhao Muqiu , Shi Zhiqiang , Luo Huijue , Cai Jiali , Han Qiuying
Published: February 2024

Introduction

The transplantation of seagrass fragments with shoots and rhizomes is the most common method for the ecological restoration of damaged seagrass meadows.

Methods

The aim of this study was to explore the effects of exogenous addition (10 mg per month for 3 months) of three commonly used plant growth regulators (PGRs), including indoleacetic acid (IAA), gibberellin (GA3), and paclobutrazol (PP333) on the growth and physiology of transplanted Thalassia hemprichii fragments (TTFs), with and without the rhizome apex (RA), using a simulation test. [Results] IAA and GA3 elevated the photosynthetic capacity and growth rate of TTF leaves but did not significantly alter leaf length and width. In contrast, PP333 reduced the leaf photosynthetic capacity and growth rate, while greatly increasing the leaf width and root viability. Additionally, PP333 treatment led to an increase in antioxidant enzyme activities (peroxidase [POD], superoxide dismutase [SOD], and catalase [CAT]), as well as malondialdehyde (MDA) and total phenol contents in TTFs, indicating some stress effects on the seagrass. Furthermore, IAA and GA3 decreased soluble sugar and protein contents and increased starch content in TTF tissues, whereas PP333 treatment elevated both nonstructural carbohydrate and soluble protein contents. The presence of RA positively affected the growth and physiology of T. hemprichii compared with TTFs without RA. There was a significant interaction between the PGRs and RA on leaf growth rate, chlorophyll fluorescence variables, and photosynthetic pigment content of the TTFs (p < 0.05).

Discussion

This study provides guidelines for the application of PGRs during the transplantation of T. hemprichii fragments for the restoration of seagrass meadows.
The effect of Te-based lead-free glass powder containing Ge and Ag+ on the contact formation and electrical performance of silicon solar cells
Authors: Yu Xianglei , Li Wei , Sun Hu , Qian Zhuo , Li Junpeng , Yu Yang , Gan Guoyou
Published: February 2024

The Te-based glass powder exhibits distinctive characteristics such as a low melting temperature and high chemical stability, rendering it a focal point of research in the realm of glass powder applications for solar cells. In this investigation, a pioneering Ge-containing Te-based lead-free glass powder was synthesized, and the influence of GeO2 content on critical parameters such as glass transition temperature (Tg), high-temperature fluidity, high-temperature wettability, acid and alkali resistance, as well as the network structure of the glass, was systematically explored. At an optimal GeO2 content of 8%, the glass powder displayed the lowest Tg (437°C), accompanied by a subdued crystallization reaction. The high-temperature fluidity and wettability exhibited favorable characteristics, indicating that the inclusion of GeO2 in the glass powder resulted in an enhanced interface contact. Building upon this foundation, techniques to augment the Ag+ content within the glass powder were investigated, along with the interaction between Ag+ and the SiNx anti-reflection layer or silicon on the surface of crystalline silicon solar cells. It was discerned that the Ag+ content in the glass powder significantly influences the deposition of silver microcrystals on the surface of crystalline silicon, thereby impacting the contact resistance of the solar cell. Then influences the series resistance and photoelectric conversion efficiency of the solar cell.
Planting grass enhances relations between soil microbes and enzyme activities and restores soil functions in a degraded grassland
Authors: Zhang Minghui , Li Zhuo , Zhang Bin , Zhang Ruohui , Xing Fu
Published: February 2024

Introduction

Forage culture is a common way to restore degraded grasslands and soil functions, in which the reconstruction of the soil microbial community and its relationship with extracellular enzyme activity (EEAs) can characterize the recovery effects of degraded grasslands. However, the impacts of forage culture on the interaction between soil microbes and EEAs and whether the recovery effect of soil functions depends on the varying degradation statuses remain unclear.

Methods

We conducted a plantation of a dominant grass, Leymus chinensis, in the soil collected from severe, moderate, light, and non-degradation statuses in the Songnen grassland in northeastern China. We measured soil microbial diversity and soil EEAs, and predicted microbial functional groups using FUNGuild.

Results

The results showed that L. chinensis culture promoted soil bacterial alpha diversity and soil EEAs only in the moderate degradation status, indicating a dramatic dependence of the recovery effects of the grass culture on degradation status of the grassland. After planting L. chinensis for 10 weeks, a decreasing trend in the chemoheterotrophy and nitrate-reduction microbial functional groups was found. In contrast, the abundance of the nitrogen (N)-fixing microbial functional group tended to increase. The positive correlation between soil EEAs and the nitrate-reduction and N-fixing microbial functional groups was enhanced by planting L. chinensis, indicating that grass culture could promote soil N cycle functions.

Conclusion

We illuminate that grass culture may promote the restoration of soil functions, especially soil N cycling in degraded grasslands, and the recovery effect may depend on the grassland degradation status. We emphasized that selection of the plant species for restoration of grasslands needs to consider the restoration effects of microbial functional groups and soil functions.
Explainable artificial intelligence for microbiome data analysis in colorectal cancer biomarker identification
Authors: Novielli Pierfrancesco , Romano Donato , Magarelli Michele , Bitonto Pierpaolo Di , Diacono Domenico , Chiatante Annalisa , Lopalco Giuseppe , Sabella Daniele , Venerito Vincenzo , Filannino Pasquale , Bellotti Roberto , De Angelis Maria , Iannone Florenzo , Tangaro Sabina
Published: February 2024

Background

Colorectal cancer (CRC) is a type of tumor caused by the uncontrolled growth of cells in the mucosa lining the last part of the intestine. Emerging evidence underscores an association between CRC and gut microbiome dysbiosis. The high mortality rate of this cancer has made it necessary to develop new early diagnostic methods. Machine learning (ML) techniques can represent a solution to evaluate the interaction between intestinal microbiota and host physiology. Through explained artificial intelligence (XAI) it is possible to evaluate the individual contributions of microbial taxonomic markers for each subject. Our work also implements the Shapley Method Additive Explanations (SHAP) algorithm to identify for each subject which parameters are important in the context of CRC.

Results

The proposed study aimed to implement an explainable artificial intelligence framework using both gut microbiota data and demographic information from subjects to classify a cohort of control subjects from those with CRC. Our analysis revealed an association between gut microbiota and this disease. We compared three machine learning algorithms, and the Random Forest (RF) algorithm emerged as the best classifier, with a precision of 0.729 ± 0.038 and an area under the Precision-Recall curve of 0.668 ± 0.016. Additionally, SHAP analysis highlighted the most crucial variables in the model's decision-making, facilitating the identification of specific bacteria linked to CRC. Our results confirmed the role of certain bacteria, such as Fusobacterium, Peptostreptococcus, and Parvimonas, whose abundance appears notably associated with the disease, as well as bacteria whose presence is linked to a non-diseased state.

Discussion

These findings emphasizes the potential of leveraging gut microbiota data within an explainable AI framework for CRC classification. The significant association observed aligns with existing knowledge. The precision exhibited by the RF algorithm reinforces its suitability for such classification tasks. The SHAP analysis not only enhanced interpretability but identified specific bacteria crucial in CRC determination. This approach opens avenues for targeted interventions based on microbial signatures. Further exploration is warranted to deepen our understanding of the intricate interplay between microbiota and health, providing insights for refined diagnostic and therapeutic strategies.
Agrobacteria deploy two classes of His-Me finger superfamily nuclease effectors exerting different antibacterial capacities against specific bacterial competitors
Authors: Santos Mary Nia M. , Pintor Katherine L. , Hsieh Pei-Yu , Cheung Yee-Wai , Sung Li-Kang , Shih Yu-Ling , Lai Erh-Min
Published: February 2024

The type VI secretion system (T6SS) assembles into a contractile nanomachine to inject effectors across bacterial membranes for secretion. The Agrobacterium tumefaciens species complex is a group of soil inhabitants and phytopathogens that deploys T6SS as an antibacterial weapon against bacterial competitors at both inter-species and intra-species levels. The A. tumefaciens strain 1D1609 genome encodes one main T6SS gene cluster and four vrgG genes (i.e., vgrGa-d), each encoding a spike protein as an effector carrier. A previous study reported that vgrGa-associated gene 2, named v2a, encodes a His-Me finger nuclease toxin (also named HNH/ENDO VII nuclease), contributing to DNase-mediated antibacterial activity. However, the functions and roles of other putative effectors remain unknown. In this study, we identified vgrGc-associated gene 2 (v2c) that encodes another His-Me finger nuclease but with a distinct Serine Histidine Histidine (SHH) motif that differs from the AHH motif of V2a. We demonstrated that the ectopic expression of V2c caused growth inhibition, plasmid DNA degradation, and cell elongation in Escherichia coli using DNAse activity assay and fluorescence microscopy. The cognate immunity protein, V3c, neutralizes the DNase activity and rescues the phenotypes of growth inhibition and cell elongation. Ectopic expression of V2c DNase-inactive variants retains the cell elongation phenotype, while V2a induces cell elongation in a DNase-mediated manner. We also showed that the amino acids of conserved SHH and HNH motifs are responsible for the V2c DNase activity in vivo and in vitro. Notably, V2c also mediated the DNA degradation and cell elongation of the target cell in the context of interbacterial competition. Importantly, V2a and V2c exhibit different capacities against different bacterial species and function synergistically to exert stronger antibacterial activity against the soft rot phytopathogen, Dickeya dadantii.
Efficacy and mechanism of acupuncture in animal models of depressive-like behaviors: a systematic review and meta-analysis
Authors: Huang Yingjie , Chen Weiping , Li Xingfu , Tan Tian , Wang Tunyi , Qiu Shishi , Li Guangyao , Yang Cong , Li Min , Duan Lining
Published: February 2024

Background

Many studies have investigated the efficacy of acupuncture in treating depression, but the mechanism of acupuncture for depression is still controversial and there is a lack of meta-analysis of mechanisms. Consequently, we investigated acupuncture’s efficacy and mechanism of depression.

Methods

We searched the Cochrane Library, PubMed, EMBASE, Web of Science. The SYRCLE Risk of Bias Tool was used to assess bias risk. Meta-analysis was performed using Stata 15.0 for indicators of depression mechanisms, body weight and behavioral tests.

Results

A total of 22 studies with 497 animals with depressive-like behaviors were included. Meta-analysis showed that acupuncture significantly increased BDNF [SMD = 2.40, 95% CI (1.33, 3.46); I2 = 86.6%], 5-HT [SMD = 2.28, 95% CI (1.08, 3.47); I2 = 87.7%] compared to the control group (p < 0.05), and significantly reduced IL-1β [SMD = −2.33, 95% CI (−3.43, −1.23); I2 = 69.6%], CORT [SMD = −2.81, 95% CI (−4.74, −0.87); I2 = 86.8%] (p < 0.05). Acupuncture improved body weight [SMD = 1.35, 95% CI (0.58, 2.11); I2 = 84.5%], forced swimming test [SMD = −1.89, 95% CI (−2.55, −1.24); I2 = 76.3%], open field test (crossing number [SMD = 3.08, 95% CI (1.98, 4.17); I2 = 86.7%], rearing number [SMD = 2.53, 95% CI (1.49, 3.57); I2 = 87.0%]) (p < 0.05) compared to the control group.

Conclusion

Acupuncture may treat animals of depressive-like behaviors by regulating neurotrophic factors, neurotransmitters, inflammatory cytokines, neuroendocrine system.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023403318, identifier (CRD42023403318).
Time-restricted feeding restores metabolic flexibility in adult mice with excess adiposity
Authors: Yan Lin , Rust Bret M. , Palmer Daniel G.
Published: February 2024

Introduction

Obesity is prevalent with the adult population in the United States. Energy-dense diets and erratic eating behavior contribute to obesity. Time-restricted eating is a dietary strategy in humans that has been advanced to reduce the propensity for obesity. We hypothesized that time-restricted feeding (TRF) would improve metabolic flexibility and normalize metabolic function in adult mice with established excess adiposity.

Methods

Male C57BL/6NHsd mice were initially fed a high-fat diet (HFD) for 12 weeks to establish excess body adiposity, while control mice were fed a normal diet. Then, the HFD-fed mice were assigned to two groups, either ad libitum HFD or TRF of the HFD in the dark phase (12 h) for another 12 weeks.

Results and discussion

Energy intake and body fat mass were similar in TRF and HFD-fed mice. TRF restored rhythmic oscillations of respiratory exchange ratio (RER), which had been flattened by the HFD, with greater RER amplitude in the dark phase. Insulin sensitivity was improved and plasma cholesterol and hepatic triacylglycerol were decreased by TRF. When compared to HFD, TRF decreased transcription of circadian genes Per1 and Per2 and genes encoding lipid metabolism (Acaca, Fads1, Fads2, Fasn, Scd1, and Srebf1) in liver. Metabolomic analysis showed that TRF created a profile that was distinct from those of mice fed the control diet or HFD, particularly in altered amino acid profiles. These included aminoacyl-tRNA-biosynthesis, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, TRF improved metabolic function in adult mice with excess adiposity. This improvement was not through a reduction in body fat mass but through the restoration of metabolic flexibility.
Case report: Enfortumab vedotin induced refractory DKA and multi organ failure – a rare fatal adverse event
Authors: Kapoor Astha Koolwal , Ellis Carleton S. , Pandey Deepali , Allison Derek B. , Myint Zin W.
Published: February 2024

There are very few therapeutic options to treat patients with locally advanced or metastatic Urothelial Cancer (UC). Enfortumab vedotin (EV) was recently approved by the FDA and has become a new therapeutic option for patients previously managed with conventional treatments. Despite its efficacy, EV carries the potential for infrequent yet severe adverse effects. In this report, we present a case of a patient undergoing EV treatment for urothelial carcinoma who developed refractory diabetic ketoacidosis (DKA) unresponsive to escalating insulin doses and necessitating continuous renal replacement therapy. While DKA was resolved, the patient eventually succumbed to progressive maculopapular skin rash, liver failure, and respiratory failure. Additionally, the study delves into a review of cases of EV-induced refractory DKA in the literature, shedding light on the similarities in patient profiles, timelines of adverse effects and the treatment strategies employed to manage the ensuing complications.
PX-478, an HIF-1α inhibitor, impairs mesoCAR T cell antitumor function in cervical cancer
Authors: Panahi Meymandi Ahmad Reza , Akbari Behnia , Soltantoyeh Tahereh , Shahosseini Zahra , Hosseini Mina , Hadjati Jamshid , Mirzaei Hamid Reza
Published: February 2024

Introduction

Chimeric Antigen Receptor (CAR) T cell therapy has demonstrated remarkable success in treating hematological malignancies. However, its efficacy against solid tumors, including cervical cancer, remains a challenge. Hypoxia, a common feature of the tumor microenvironment, profoundly impacts CAR T cell function, emphasizing the need to explore strategies targeting hypoxia-inducible factor-1α (HIF-1α).

Methods

In this study, we evaluated the effects of the HIF-1α inhibitor PX-478 on mesoCAR T cell function through in-silico and in vitro experiments. We conducted comprehensive analyses of HIF-1α expression in cervical cancer patients and examined the impact of PX-478 on T cell proliferation, cytokine production, cytotoxicity, and exhaustion markers.

Results

Our in-silico analyses revealed high expression of HIF-1α in cervical cancer patients, correlating with poor prognosis. PX-478 effectively reduced HIF-1α levels in T and HeLa cells. While PX-478 exhibited dose-dependent inhibition of antigen-nonspecific T and mesoCAR T cell proliferation, it had minimal impact on antigen-specific mesoCAR T cell proliferation. Notably, PX-478 significantly impaired the cytotoxic function of mesoCAR T cells and induced terminally exhausted T cells.

Discussion

Our results underscore the significant potential and physiological relevance of the HIF-1α pathway in determining the fate and function of both T and CAR T cells. However, we recognize the imperative for further molecular investigations aimed at unraveling the intricate downstream targets associated with HIF-1α and its influence on antitumor immunity, particularly within the context of hypoxic tumors. These insights serve as a foundation for the careful development of combination therapies tailored to counter immunosuppressive pathways within hypoxic environments and fine-tune CAR T cell performance in the intricate tumor microenvironment.
Successful reimplantation of extruded bone segment in lower limb open fractures: case report and literature review
Authors: Hu Xiongke , Tan Qian , Zhu Guanghui , Liu Kun
Published: February 2024

Objective

The aim of this study is to summarize and demonstrate the different sterilization methods and surgical techniques for open fractures with impacted bone segments in the lower limbs.

Methods

A retrospective analysis was conducted on the clinical characteristics, treatment methods, and outcomes of a case involving a 10.5 cm extruded segment of the femur in a 9-year-old male with a right femoral comminuted fracture treated at our center. Additionally, a retrospective review and summary were conducted on all reported cases of open fractures with impacted bone segments in the lower limbs.

Results

Our center treated a 9-year and 11-month-old male child who presented with a Gustilo type IIIB open fracture of the femur along with a large segment of the femur being ejected as a result of a car accident. The child was resuscitated to correct hypovolemic shock, underwent emergency wound debridement, and had Ilizarov external fixation of the femur. The ejected femur segment was sterilized using ethylene oxide and re-implanted four days after the injury. A literature review showed that out of the cases of open fractures with impacted bone segments in the lower limbs, there were 14 cases involving the femur and 5 cases involving the tibia. Among them, sterilization was performed using povidone-iodine in 6 cases, high-pressure steam sterilization in 3 cases, and other methods including gamma-ray irradiation and soaking in antibacterial solution were used in the remaining cases. In terms of surgical methods, 7 cases were fixed with locking plates, 3 cases were fixed with external fixation devices, 1 case was immobilized in a cast, 1 case was fixed with an intramedullary rod, and 4 cases involved a combination of external fixation and internal fixation. The average time for re-implantation was 7.6 days after the injury. There were no serious complications such as infection or non-union observed in any of the cases during follow-up.

Conclusion

Ethylene oxide can be considered a reliable choice for the reimplantation of displaced bone segments in open fractures after sterilization.
Immunoglobulin replacement therapies in inborn errors of immunity: a review
Authors: Sil Archan , Basu Suprit , Joshi Vibhu , Pilania Rakesh Kumar , Siniah Sangeetha , Suri Deepti , Rawat Amit , Singh Surjit
Published: February 2024

Immunoglobulins (Ig) were used as a therapeutic modality for the first time in a patient with X-linked agammaglobulinemia in 1952 by Colonel Ogden Bruton, decades before the molecular mechanisms causing the disease were unraveled. In many autoimmune and inflammatory illnesses, human immunoglobulin has been employed as a significant immunomodulatory and immunosuppressive drug. In patients with inborn errors of immunity (IEI), immunoglobulin remains a cornerstone of management. IEIs are notable causes of recurrent infections and autoimmunity due to inheritable single-gene defects in genes encoding for different components of the immune system. As there is decreased immunoglobulin production in IEIs with antibody defects, immunoglobulin replacement is the mainstay of therapy in these disorders. Although serum immunoglobulin levels may not be low in combined immune defects, immunoglobulin replacement is still necessary in these disorders due to a deficiency of functional antibodies and qualitative defects of immunoglobulins. Commercial immunoglobulin preparations are generated from plasma donated by thousands of donors. Immunoglobulin preparations are usually available in two forms: intravenous and subcutaneous immunoglobulins. In the developed world, both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) are available, and SCIg is preferred over IVIg for replacement therapy in patients with IEIs. In developing countries, IVIg remains the mainstay of replacement therapy. The rate of adverse events has significantly reduced over the last few years due to advancements in the production process. In this review article, we discuss different aspects of the use of Ig (indications, dosing, mechanism of action, route, adverse effects) in patients with IEIs.
Anticancer therapy-induced adverse drug reactions in children and preventive and control measures
Authors: Yan Hui , Wang Penggao , Yang Fang , Cheng Weyland , Chen Congcong , Zhai Bo , Zhou Yang
Published: February 2024

In recent years, considerable achievements have been made in pediatric oncology with the innovation and development of antitumor drugs. However, compared to adults, children as a special group have not yet matured fully in terms of liver and kidney function. Moreover, pediatric patients are prone to more adverse drug reactions (ADRs) from the accumulation of antineoplastic drugs due to their smaller body size and larger body surface area. Chemotherapy-related ADRs have become a non-negligible factor that affects cancer remission. To date, studies on ADRs in pediatric cancer patients have emerged internationally, but few systematic summaries are available. Here, we reviewed the various systemic ADRs associated with antitumor drugs in children and adolescent patients, as well as the advances in strategies to cope with ADRs, which consisted of neurotoxicity, hematological toxicity, cardiotoxicity, ADRs of the respiratory system and gastrointestinal system and urinary system, ADRs of the skin and its adnexa, allergic reactions, and other ADRs. For clinicians and researchers, understanding the causes, symptoms, and coping strategies for ADRs caused by anticancer treatments will undoubtedly benefit more children.
Application of calcium overload-based ion interference therapy in tumor treatment: strategies, outcomes, and prospects
Authors: Li Shuangjiang , Fan Ruicheng , Wang Yuekai , He Kunqian , Xu Jinhe , Li Hongli
Published: February 2024

Low selectivity and tumor drug resistance are the main hinderances to conventional radiotherapy and chemotherapy against tumor. Ion interference therapy is an innovative anti-tumor strategy that has been recently reported to induce metabolic disorders and inhibit proliferation of tumor cells by reordering bioactive ions within the tumor cells. Calcium cation (Ca2+) are indispensable for all physiological activities of cells. In particular, calcium overload, characterized by the abnormal intracellular Ca2+ accumulation, causes irreversible cell death. Consequently, calcium overload-based ion interference therapy has the potential to overcome resistance to traditional tumor treatment strategies and holds promise for clinical application. In this review, we 1) Summed up the current strategies employed in this therapy; 2) Described the outcome of tumor cell death resulting from this therapy; 3) Discussed its potential application in synergistic therapy with immunotherapy.
Influence of surface water and groundwater on functional traits and trade-off strategies of oasis communities at the end of the Keriya River, China
Authors: Shi Haobo , Shi Qingdong , Zhou Xiaolong , Cui Chuandeng , Li Xiang , Zhang Zipeng , Zhu Chuanmei
Published: February 2024

Plant functional traits reflect the capacity of plants to adapt to their environment and the underlying optimization mechanisms. However, few studies have investigated trade-off strategies for functional traits in desert-wetland ecosystems, the mechanisms by which surface water disturbance and groundwater depth drive functional trait variation at the community scale, and the roles of intraspecific and interspecific variation. Therefore, this study analyzed specific differences in community-weighted mean traits among habitat types and obtained the relative contribution of intraspecific and interspecific variation by decomposing community-weighted mean traits, focusing on the Daliyabuyi Oasis in the hinterland of the Taklamakan Desert. We also explored the mechanisms by which surface water and groundwater influence different sources of variability specifically. The results showed that plant height, relative chlorophyll content, leaf thickness, leaf nitrogen content, and nitrogen-phosphorus ratio were the key traits reflecting habitat differences. As the groundwater depth becomes shallower and surface water disturbance intensifies, plant communities tend to have higher leaf nitrogen content, nitrogen-phosphorus ratio, and relative chlorophyll content and lower height. Surface water, groundwater, soil water content, and total soil nitrogen can influence interspecific and intraspecific variation in these traits through direct and indirect effects. As arid to wet habitats change, plant trade-off strategies for resources will shift from conservative to acquisitive. The study concluded that community functional traits are mainly contributed by interspecific variation, but consideration of intraspecific variation and the covariation effects that exist between it and interspecific variation can help to further enhance the understanding of the response of community traits in desert-wetland ecosystems to environmental change. Surface water disturbance has a non-negligible contribution to this adaptation process and plays a higher role than groundwater depth.
Modeling bacterial microcompartment architectures for enhanced cyanobacterial carbon fixation
Authors: Trettel Daniel S. , Pacheco Sara L. , Laskie Asa K. , Gonzalez-Esquer C. Raul
Published: February 2024

The carboxysome is a bacterial microcompartment (BMC) which plays a central role in the cyanobacterial CO2-concentrating mechanism. These proteinaceous structures consist of an outer protein shell that partitions Rubisco and carbonic anhydrase from the rest of the cytosol, thereby providing a favorable microenvironment that enhances carbon fixation. The modular nature of carboxysomal architectures makes them attractive for a variety of biotechnological applications such as carbon capture and utilization. In silico approaches, such as molecular dynamics (MD) simulations, can support future carboxysome redesign efforts by providing new spatio-temporal insights on their structure and function beyond in vivo experimental limitations. However, specific computational studies on carboxysomes are limited. Fortunately, all BMC (including the carboxysome) are highly structurally conserved which allows for practical inferences to be made between classes. Here, we review simulations on BMC architectures which shed light on (1) permeation events through the shell and (2) assembly pathways. These models predict the biophysical properties surrounding the central pore in BMC-H shell subunits, which in turn dictate the efficiency of substrate diffusion. Meanwhile, simulations on BMC assembly demonstrate that assembly pathway is largely dictated kinetically by cargo interactions while final morphology is dependent on shell factors. Overall, these findings are contextualized within the wider experimental BMC literature and framed within the opportunities for carboxysome redesign for biomanufacturing and enhanced carbon fixation.
Biochemical analysis of the TPS-a subfamily in Medicago truncatula
Authors: Hendrickson Hannah , Islam Monirul , Wabo Ghislain Fotso , Mafu Sibongile
Published: February 2024

Terpenes are important mediators of plant chemical response to environmental cues. Here, we describe the genome-wide identification and biochemical characterization of TPS-a members in Medicago truncatula, a model legume crop. Genome mining identified thirty-nine full-length terpene synthases with a significant number predicted to produce monoterpenes and sesquiterpenes. Biochemical characterization of the TPS-a subfamily associated with sesquiterpene biosynthesis revealed such compounds, that exhibit substantial biological activity in other plants. Gene expression analysis using qPCR and the Medicago gene atlas illustrated distinct tissue and time-based variation in expression in leaves and roots. Together our work establishes the gene-to-metabolite relationships for sesquiterpene synthases in M. truncatula. Understanding the biosynthetic capacity is a foundational step to defining the ecological roles of this important family of compounds.
How does problem-solving pedagogy affect creativity? A meta-analysis of empirical studies
Authors: Zhan Zehui , He Luyao , Zhong Xuanyan
Published: February 2024

The purpose of this study was to investigate the effects of problem-solving pedagogy on individual students’ creativity in different teaching contexts and conditions, and to examine the role of moderating variables that may affect the overall effect size. The study screened 19 relevant studies from the Web of Science for inclusion in the meta-analysis, and extracted 77 effect sizes from these studies that could be used in the meta-analysis. The study first explored the relationship between problem-solving pedagogy and the development of learner creativity, and further analysis focused on moderating variables to investigate the effects of instructional method, grouping method, grade level, problem-solving scaffolding, source of problems, the application of thinking tools, and the application of technology. The results showed that problem-solving pedagogy enhances students’ creativity, while at the same time, among the sources of problems, student-discovered problems are most conducive to creativity stimulation, while teacher-determined problems and problems that lead to student discovery are less effective in terms of promoting creativity. Among the grouping methods, heterogeneous grouping can better utilize the creativity cultivation effect of the problem-solving pedagogy than random grouping and homogeneous grouping. Among the different levels of grades, learners in elementary school are better able to gain creativity under the influence of problem-solving pedagogy than learners in middle school, high school, college, and those in on-the-job learning. However, this study did not reveal any significant benefits for creativity enhancement under the four conditions of instructional method, problem-solving scaffolding, thinking tools-assisted, or technology. The results of this study clarify the importance of problem-solving pedagogy for creativity development, and also reveal the actual effects of the various ways of applying problem-solving pedagogy on creativity development as well as the problems that exist, which provides inspiration for how to better utilize problem-solving pedagogy in the future.