bluuebunny/crossref_metadata_2025 huggingface dataset:
DTPA-Receptor – A novel reporter gene system for the specific and sensitive PET imaging of CAR-T cells and AAV transduced cells
Authors: Weber Wolfgang , Morath Volker , Fritschle Katja , Warmuth Linda , Anneser Markus , Dötsch Sarah , Zivanic Milica , Krumwiede Luisa , Bösl Philipp , Bozoglu Tarik , Robu Stephanie , Libertini Silvana , Kossatz Susanne , Kupatt Christian , Schwaiger Markus , Steiger Katja , Busch Dirk , Skerra Arne
Published: August 2023

Advanced Therapy Medicinal Products (ATMPs), such as cell and gene therapies, necessitate a reliable diagnostic method for quantitative monitoring. We developed a novel reporter gene system for PET imaging consisting of a membrane-anchored Anticalin protein (DTPA-R) that acts as a high-affinity receptor for the radioligand [18F]F-DTPA•TbIII. The reporter protein shows high cell surface expression of up to ~1×106 receptors per cell. After systemic administration, the pharmacologically inert radioligand rapidly clears via the renal route and, at t=90 min, generates a strong signal of 22.1 %ID/g for DTPA-R-expressing PC3 cells compared to 0.2 %ID/g for DTPA-R-negative controls (ratio: 125). The detection limit for JurkatDTPA-R cells was 500 cells in a PET phantom ex vivo and 8,000 if subcutaneously injected. In vivo expansion and migration of CD19-CAR-TDTPA-R cells was successfully monitored over four weeks with a linear relationship between PET signal and CAR-T cell number. Furthermore, our reporter system allowed quantitative and longitudinal imaging of AAV9 viral vectors with a linear dose-to-signal relation. In summary, DTPA-R shows high potential for in vivo monitoring of ATMP-based therapies.
Validation of the Patient Reported Experiences and Outcomes of Safety in Primary Care Compact Form Brazil
Authors: Silva Ana Elisa Bauer Camargo , Sousa Tanielly Paula , Guimaraes Rafael Alves , Pagotto Valéria , Lima Juliana Carvalho , Sousa Maiana Regina Gomes
Published: August 2023

Objective
to analyze the psychometric properties of the cross-culturally adapted version of the Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) Compact Form Brazil.
Methods
a methodological study was conducted with 281 adult Primary Health Care users. Data collection took place online. Confirmatory factor analysis (CFA) was used to evaluate the psychometric properties of the PREOS-PC after the process of cross-cultural adaptation to the Brazilian context. Internal consistency was evaluated through Cronbach’s alpha coefficient (α) and McDonald’s omega coefficient (ω).
Results
the sample consisted of 73.3% women. The mean age was 36.3 years (SD = 12.2). Of the 23 items of the PREOS-PC that were eligible for CFA, a model with four correlated domains and 16 items presented satisfactory fit indexes. The domains were Practice Activation (PrA) (four items), Patient Activation (PaA) (two items), Experiences of patient safety events (EPaS) (five items) and Outcomes of patient safety (OPaS) (six items). One domain (GPeS) presented one question with a 0 to 10 response scale and two open questions, which cannot be inserted in the CPA due to the nature of the items, but can be included in the application of the scale, being evaluated individually. In this factorial model, five items (EPaS2, EPaS3, EPaS4, EPaS5, EPaS6 and EPaS8) presented factor loadings ≤ 0.30. The α and ω values demonstrated good internal consistency for all domains of the PREOS-CP.
Conclusions
the Brazilian version of the PREOS-PC Compact Form Brazil composed of four domains (PrA, PA, EPaS and OPaS) and 16 items presented evidence of validation of its psychometric properties and can be used to evaluate the experiences and results of patient safety in Primary Health Care in the Brazilian context.
Chitosan isolated, purified and characterized from Shrimp Shell Waste used in Clove Essential Oil-loaded Chitosan Alginate nano-encapsulation.
Authors: Ahmed Habiba Abdelaziz , Salama Zeinab A. , Nassrallah Amr
Published: August 2023

Chitosan is a polysaccharide polymer widely applied in biomedical and medicinal fields due to its biological properties, such as being antimicrobial, biodegradable in the human body, and nontoxic. Clove essential oil is well known for its antimicrobial, anticancer, antiviral, and antioxidant properties. However, essential oils are known to be insoluble in water, unstable, and volatile. Therefore, the present study focuses on two main objectives: The first main emphasis is obtaining low-cost extraction, purification, and characterization of chitosan from shrimp shells waste using the three phases of demineralization, deproteinization, and deacetylation. The second point focused on using isolated chitosan from shrimp shell waste as a polymer to enhance the biological and physical characteristics of the clove essential oil from its natural property by means of encapsulation form. The isolated chitosan was characterized using a scanning electron microscope (SEM), FTIR spectroscopy, x-ray, and thermo gravimetric analysis. The results illustrated that the isolated Chitosan has thermal stability. Also, the produced clove essential oil nano-capsules were characterized using GC mass, FTIR and zeta seizer. The data showed that the particle size, pdi, and zeta potential were 8.4 nm, 0.6 mV, and 12.9 mV, respectively.
Enhanced THz Emission from Photo-ConductiveAntennas by integrating photonic structures onSemi-insulating GaAs substrate
Authors: Rana Goutam , Gupta Abhishek , Bhatacharya Arkabrata , Duttagupta Siddhartha Prakash , Prabhu Shriganesh S.
Published: August 2023

Tera Hertz Photoconductive antennas has provided a great momentum to the THz research with features like room temperature,broad band operation with reasonably low cost both as emitters and detectors. The main drawback though remained the limitedpower output resulting from a low conversion efficiency. In this article we have demonstrated that the efficiency can be greatlyimproved (∼200%) by incorporating sub-micron photonic structures on the surface. The photonic structure on the surfacenot only contribute to better coupling of pump beam resulting in increased photo-carriers but also in effective recombinationof the carriers after generation of THz and suppresses the carrier screening to a great extent. Experimental and Numericalstudies were used to establish the enhanced photo-carrier generation and it’s subsequent controlled transport in a defect fullpath leading to reduced screening. The photonic structures can be extended to Large Area Emitter (LAE) to develop emitters/detectors for real life THz systems to be designed for out of laboratory conditions. Currently, commercial LAEs use Plasmonicsstructure or anti-reflection coating which comes with lots of limitations which can easily be overcome by the proposed methodin the article.
Cathepsin C inhibition reduces neutrophil serine protease activity and improves activated neutrophil-mediated disorders
Authors: Ishizu Akihiro , Nishibata Yuka , Arai Suishin , Taniguchi Mai , Nakade Issei , Ogawa Hodaka , Kitano Shota , Hosoi Yumeka , Shindo Ayano , Nishiyama Ryo , Masuda Sakiko , Nakazawa Daigo , Tomaru Utano , Shimizu Takafumi , Sinko William , Nagakura Tadashi , Terada Yoh
Published: August 2023

Cathepsin C (CatC) is an enzyme which regulates the maturation of neutrophil serine proteases (NSPs) essential for neutrophil activation. Activated neutrophils are key players in the innate immune system, and are also implicated in the etiology of various inflammatory diseases. This study aims to demonstrate a therapeutic potential for CatC inhibitors against disorders in which activated neutrophil-derived neutrophil extracellular traps (NETs) play a significant role. We developed a novel CatC inhibitor, MOD06051, which dose-dependently suppressed the cellular activity of NSPs, including neutrophil elastase (NE), in vitro. Next, neutrophils derived from MOD06051-administered rats were evaluated for NE activity and NET-forming ability, with results significantly lower than controls. Furthermore, MOD06051 dose-dependently ameliorated vasculitis and significantly decreased NETs when administered to a rat model of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody-associated vasculitis (AAV). These findings suggest that CatC inhibition is a promising strategy to reduce neutrophil activation and improve activated neutrophil-mediated diseases such as MPO-AAV.
Ultrasound-driven nanosilicon transfected tobacco cell as robust factory for collagen III protein synthesis
Authors: Gu Tingwei , Zhou Nan , Xu Yang , Liu Yuda , Tan Minhong , Liu Jianxiang , Peng Lihua
Published: August 2023

Background: Therapeutic protein is one of the mostly used medications and the transgenic plant system offers an alternative to synthesis protein with simple practice and reduced infection issues. However, conventional plant transforming vehicles such as agrobacterium and electroporation have been hampered by limited transformation efficiency and biorisk.
Methods: Herein, we describe an ultrasound driven nanosilicon composed hybrid-nanoplatform (named as UDSP), which can transform tobacco cells with high efficiency following a simple protocol.
Results: With plasmid DNA encoding collagen III gene as a representative, UDSP demonstrates excellent transfection efficiency in tobacco cells with high efficacy to produce collagen III protein, with considerable number of exosomes containing collagen III (Col-Exo) produced simultaneously. The synthesized collagen III protein and Col-Exo are demonstrated for the obvious therapeutic effects in promoting wound regeneration and inflammation alleviation.
Conclusions: UDSP transfected tobacco cell is shown as a promising biofactory with efficacy to synthesize recombinant proteins with intact tertiary structure, and therapeutic exosomes with target protein incorporated, with great potential in the protein synthesis and bioengineering.
Statistical analysis of Low latitude Spread F at the American, Atlantic and Pacific sectors using digisonde observations
Authors: Bhaneja Preeti , Klenzing Jeff , Pachecho Edgardo E , Earle Greg , Bullett Terry
Published: August 2023

Digisonde data from three different longitude sectors from Jicamarca (12°S, 76.8°W, -2.5° declination angle) from 2001–2016, Ascension Island (7.9°S, 14.4°W, -15.09° declination angle) from 2000–2014, Kwajalein (8.71°N, 167.7°E, 7.5° declination angle) from 2004–2012, has been processed and analyzed to determine statistical studies of equatorial spread F, a diagnostic of irregular plasma structure in the ionosphere. A new method of spread F detection for low latitude region is used to determine solar and seasonal variation over these three sites. An algorithm has been developed to detect the foF2 and hmF2 values from an ionogram and this has been validated using manually scaled ionograms, as well as comparisons to the SAMI2 and IRI models.
Area Specific Monitoring of Stratum Corneum Hydration and Transepidermal Water Loss among Atopic Dermatitis Patients
Authors: Kwon Bo Yeon , Kim Dohyeong , Shim Kyungmin , Nguyen Cindy , Lee Hee Chul , Kang Daeshik , Kim Hohyun , Seo Sungchul
Published: August 2023

SCORAD is widely used to assess the severity of atopic eczema, but score systems based on the entire body may be limited in effective monitoring and intervention. It is crucial to monitor moisture levels in affected body part, but empirical research is still lacking. We analyzed the levels of stratum corneum hydration (SCH) and transepidermal water loss (TEWL) in 98 atopic dermatitis (AD) patients under the age of 10 at 15 body sites. Patients were also assessed with SCORAD and for the presence of atopic lesions at each body site. About 50-60% of AD patients had lesions in the antecubital fossa and popliteal fossa, with corresponding low SCH levels and high TEWL in the upper body. The differences in TEWL between the control group and AD patients were confirmed significant in the neck and antecubital fossa regions, while differences in SCH were identified in the face, antecubital fossa and popliteal fossa regions. A higher TEWL was found among AD patients with atopic lesions in the face and ankle. This study suggests continuous monitoring of SCH and TEWL levels at specific body sites can help identifying vulnerable body areas to atopic dermatitis, which supplements SCORAD for effective clinical intervention and prevention.
Characteristics of Gut Microbiota in Captive Asian Elephants (Elephas maximus) from Infant to Elderly
Authors: Klinhom Sarisa , Sriwicha Sirawit , Kerdphoo Sasiwan , Khonmee Jaruwan , Chattipakorn Nipon , Chattipakorn Siriporn C , Thitaram Chatchote
Published: August 2023

Gut microbiota play an important role in the health and disease in captive Asian elephants, however, its characteristics at each stage of life have not been thoroughly investigated. This study, therefore, aimed to characterize the profiles of the gut microbiota of captive Asian elephants from infants to the elderly. The diversity of the gut microbiota was lowest in infants, stable during adulthood, and slightly decreased in the geriatric period. Gut microbiota were identified by 16S rRNA sequencing from the feces of captive Asian elephants with varying age groups, including infant calves, suckling calves, weaned calves, subadult and adult elephants, and geriatric elephants. The gut microbiota of the infant elephants was dominated by milk-fermenting taxa. The fiber-fermenting taxa emerged in suckling elephants. The stabilization of gut microbiota profiles has been observed after weaning until the adult period. However, the composition of the gut microbiota was found to change again in geriatric elephants. Understanding of the composition of the gut microbiota of captive Asian elephants at each stage of life could be beneficial to support good health during each period of the elephant's lifespan.
A unique record of rock glacier kinematics and glacier interactions from the Swiss National Park spanning more than 100 years
Authors: Manchado Alberto Muñoz-Torrero , Allen Simon , Cicoira Alessandro , Wiesmann Samuel , Haller Ruedi , Stoffel Markus
Published: August 2023

The rock glaciers of the Swiss National Park were the first in the world where in-situ measurements of surface displacement were undertaken, starting with the pioneering work of Chaix in 1918. This globally unique long-term record is a main reason why these rock glaciers have recently been ordained by UNESCO as one of the top 100 IUGS geological world heritage sites. With our work we have filled the gap previously existing between the measurements from the early 20th century and the most recent measurements made over the last two decades. Through the application of photogrammetric techniques, we use this unique record spanning more than a century to geomorphologically analyze the spatiotemporal evolution of rock glaciers in the region, and to disentangle the interplay with their contributing glaciers. We show that these rock glaciers are in different phases of degradation with a general trend of deceleration and loss of volume. We observe how changes in kinematics seem to be historically controlled by the hydrological contribution of their nearby glaciers, with which they have been in close contact since the end of the Little Ice Age, but which are now severely degraded.
Barriers to and enablers of cervical cancer screening delivery in Eswatini
Authors: Khumalo Phinda Goodwill , White Jennifer , Mackenzie Lisa , Carey Mariko
Published: August 2023

Background
In 2018, Eswatini had the highest age-standardised incidence of cervical cancer in the world. The key preventive approach in Eswatini involves cervical cancer screening, delivered through the Ministry of Health and collaborations with external non-governmental organisations. However, screening rates remain low due to delivery and uptake challenges. Limited research has focused on nurses’ perspectives regarding the barriers and enablers of screening delivery, leaving gaps in knowledge. This study employed the Micro-Meso-Macro framework to explore nurses' experiences and perceptions regarding barriers and enablers to delivering screening services in Eswatini.
Methods
An interpretative qualitative design was employed. Twenty in-depth telephone interviews were conducted among 20 nurses from 20 healthcare clinics distributed across the four geographic regions of Eswatini. Data were analysed using an inductive thematic approach with constant comparison. Identified themes informed continuing data collection, and sampling continued until thematic saturation was achieved.
Results
Results are presented under three identified themes: (1) Nurses experience limited leadership and engagement from the Eswatini Ministry of Health, (2) nurses face process, resource and/or capacity barriers, and (3) client-related barriers to equity of access to screening hinder nurses' efforts to provide cervical cancer screening services. Barriers to screening service delivery include gaps in nurses’ knowledge and skills, inadequate cooperation between the Ministry of Health and non-governmental organisation-employed nurses, shortages of staff and equipment, limited training, absence of record-keeping systems, poor coordination between clinics and regional hospitals, insufficient leadership and engagement from the Ministry of Health, and lack of feedback on service delivery. Enablers of cervical cancer screening included guidelines and standard operating procedures, supportive supervision, a triage system to guide clients to screening services, comprehensive training programs, and patient incentives to promote the uptake of screening services.
Conclusions
This study identified multiple challenges in delivering cervical cancer screening services in Eswatini, spanning micro, meso, and macro levels. These challenges included nurses' lack of knowledge and skills, resource shortages, limited leadership, and dependence on NGO support. Addressing these barriers calls for a multifaceted approach, involving advocacy, better data management, supportive supervision, and educational initiatives to enhance screening services delivery.
RTCP detection method for a 5-DOF hybrid machining robot
Authors: Tian Wenjie , Guo Xu , Zhang Xiangpeng , Yang Junhao , Wang Lina
Published: August 2023

This paper mainly studies the application of RTCP testing theory and technology in hybrid robots. Firstly, based on multi-objective optimization algorithms, the RTCP testing center position and maximum testing attitude angle of the robot are obtained, so as to maximize the corresponding active joint motion range of the robot in joint space. Then, three standard RTCP test trajectories and an optimized 8-shape trajectory were designed and planned. Finally, calculate the minimum curvature radius of the RTCP trajectory, determine the maximum interpolation step size of the NC command, and generate corresponding NC commands based on the planned test trajectory for RTCP accuracy testing experiments of hybrid robots. The experimental results show that the RTCP method based on kinematic calibration can effectively detect the dynamic error of hybrid robots by detecting end position errors, thereby evaluating the five-axis linkage accuracy of hybrid robots.
Hedonic perception group intervention in adolescent depression: a randomized controlled trial
Authors: Huang Zhen , Tao Mengjun , Li Jinyan , Cheng Jia
Published: August 2023

Evidence from the pleasure perception community has been applied primarily to adults with anxiety and depression. Less is known about the effects of depression and anxiety in adolescents.To determine the efficacy of pleasure perception combined with standard therapy in the treatment of adolescent depression.Participants with ICD-10-diagnosed depression (n = 108) were randomized to receive hedonic perception group therapy combined with standard care (2 weeks, 10 treatments) and the control group received only standard care and were followed up at baseline, 2 weeks (postintervention) and 7 weeks with clinical measures that included depression, anxiety, and somatic symptoms.In the analysis of missing data by maximization, there were significant differences in GAD-7 (P < 0.01), PHQ-9, and PHQ-15 (P < 0.001) between and within groups between the experimental and control groups at 2 and 7 weeks of follow-up. Participants in the experimental group showed better treatment outcomes, and the effect size (Cohen d) of the experimental group was greater than that of the control group. The effective remission rate of the pleasure perception group plus standard treatment group was significantly higher than that of the standard treatment group alone (P < 0.05).The combination of pleasure perception groups and standard treatment is an effective treatment method for adolescent depression, which shows certain clinical application prospects.
Media Matters: Culture Medium-Dependent Hypervariable Phenotype of Mesenchymal Stromal Cells
Authors: Fitzgerald Joan C. , Shaw Georgina , Murphy J Mary , Barry Frank
Published: August 2023

Background
Despite a long history of investigation and sustained efforts in clinical testing, the number of market authorisations for mesenchymal stromal cell (MSC) therapies remains limited, with none approved by the United States Food and Drug Administration (FDA). Several barriers are impeding the clinical progression of MSC therapies, to the forefront of these is a lack of standardised manufacturing protocols which is further compounded by an absence of biologically meaningful characterisation and release assays. A look at clinical trial registries demonstrates the diversity of MSC expansion protocols with variabilities in cell source, isolation method and expansion medium, amongst other culture variables, making it extraordinarily difficult to compare study outcomes. Current identification and characterisation standards are insufficient; they are not specific to MSCs and do not indicate cell function or therapeutic action.
Methods
This work analysed the influence of five widely used culture media formulations on the colony forming potential, proliferation kinetics, trilineage differentiation potential and immunomodulatory potential of human bone marrow derived MSCs (BM-MSCs). The surface marker expression profiles were also characterised using a high-content flow cytometry screening panel of 243 markers.
Results
Significant differences in the biological attributes of BM-MSCs including clonogenicity, proliferation, differentiation propensity and immunomodulatory capacity were revealed in response to the composition of the culture medium. Despite their biological differences, all cell preparations uniformly and strongly expressed the standard positive markers proposed for BM-MSCs; CD73, CD90 and CD105. Immunophenotypic profiling revealed that the culture medium also had a significant influence on the surface proteome, with one third of tested markers exhibiting variable expression profiles. Principal component analysis demonstrated that BM-MSCs isolated and expanded in a proprietary xeno- and serum-free medium displayed the most consistent cell phenotypes with little variability between donors compared to platelet lysate (PL) and fetal bovine serum (FBS)-containing media.
Conclusions
These data suggest that media composition has a highly significant impact on the biological attributes of MSCs, but standard surface marker tests conceal these differences. The results indicate a need for (1) standardised approaches to manufacturing, with an essential focus on defined media and (2) new biologically relevant tests for MSC characterisation and product release.
A k-nearest neighbor query method of privacy protection for university library's self-built featured database based on real time national secret algorithm
Authors: Wu Nan
Published: August 2023

In order to avoid privacy information leakage, a k-nearest neighbor query method of privacy protection for university libraries' self-built featured databases based on the national secret algorithm is studied. Through a parallel clustering algorithm based on grid density and locally sensitive hash functions, hash quantization processes the original dataset in the self-built featured database to obtain average bucket clustering results; Based on the average bucket label, a secure index structure for a one-way dictionary is established to generate a key for encrypting and decrypting the subset of data managed in each average bucket through the SM4 algorithm and SM2 algorithm in the hybrid national security algorithm. Using the secure index structure of a one-way dictionary and the key generated by the national secret algorithm, it can quickly search for k-nearest neighbors of privacy protection and efficiently add, delete, and modify data in the featured database built by university libraries. The experiment proves that this method can effectively encrypt and decrypt the data in the featured database built by university libraries, and achieve the k-nearest neighbor query of privacy protection for the featured database; In different data dimensions, the k-nearest neighbor query efficiency of this method is faster; For different databases, the maximum query inflation of this method is around 9.1, which is within a reasonable range, that is, the security of k-nearest neighbor queries is better.
Stress-resilience in Parkinson's disease: predictors and associations with symptom progression
Authors: Heide Anouk van der , Dommershuijsen Lisanne , Puhlmann Lara , Kalisch Raffael , Bloem Bastiaan , Speckens Anne , Helmich Rick
Published: August 2023

Background: People with Parkinson’s disease (PD) are very sensitive to psychological stress, but not everybody reacts the same to adversity. The ability to maintain mental health despite adverse events has been conceptualized as stress-resilience. It is unclear whether stress-resilience in PD is predominantly determined by dopamine deficiency, psychosocial factors, or both. In animal models of PD, chronic stressors accelerate disease progression, but evidence in humans is lacking.
Objectives: (1) Distinguish stress-reactive from stress-resilient PD patients, (2) identify predictors for stress-resilience (resilience factors), and (3) compare symptom progression between stress-reactive and resilient patients.
Methods: We conducted a longitudinal survey in Personalized Parkinson Project participants (N=350 PD). The COVID-19 pandemic was used as a model of a stressor that was aligned in time for the entire cohort. COVID-19-related stressors, perceived stress, and severity of PD symptoms were assessed at 11 timepoints (April-October 2020). In 322 patients, both pre-COVID and in-COVID objective clinical assessments were available. We quantified individual stressor-reactivity as the residual between actual and predicted perceived stress relative to COVID-19-related stressors, and modeled trajectories of stressor-reactivity across timepoints. We explored pre-COVID predictors of 6-month average stressor-reactivity and tested whether high/low average stressor-reactivity was prospectively associated with one-year clinical progression rates.
Results: Latent class trajectory models distinguished patients with high (N=227) or low (N=123) stressor-reactivity. Pre-existing anxiety, rumination and non-motor symptom severity predicted high stressor-reactivity (risk factors), whereas quality of life, social support, positive appraisal style and cognitive abilities predicted low stressor-reactivity (resilience factors). PD-specific factors, such as disease duration, motor symptom severity and levodopa use, did not predict stressor-reactivity. During the pandemic, motor symptom progression was not accelerated, but depressive symptoms increased specifically in stress-reactive patients.
Conclusion: High stressor-reactivity in PD relates to non-motor symptoms and psychosocial factors, rather than to PD-specific factors. Stressor-reactivity is associated with larger increases in depression but not motor symptoms during follow-up.
Melatonin relieves the S-nitrosylation of plasma membrane H+-ATPase 2 to enhance saline-alkali tolerance in tomato
Authors: Gong Biao , Wei Jin-Wei , Liu Minghui , Cao Bili , Shan Qing , Liu Xiaoqian , Liu Wei , Shi Qinghua , Liu Derui
Published: August 2023

Soil salinity-alkalinity is a global problem with special relevance to land resources. Although melatonin confers multiple tolerances to plants, its role in saline-alkali tolerance remains unclear. Here, we found that excess nitric oxide (NO) accumulation accounts for saline-alkali stress by genetically manipulating the NO metabolic enzyme of S-nitrosoglutathione reductase (GSNOR). A caffeic acid O-methyltransferase (COMT) was identified to enhance melatonin synthesis and NO scavenging to improve saline-alkali tolerance. As a target protein participating in saline-alkali tolerance, plasma membrane H+-ATPase 2 (HA2) was identified to be S-nitrosylated at Cys206. Further, the S-nitrosylation of HA2 was induced by saline-alkali stress, and was aggravated by GSNOR-knockdown, but was alleviated by COMT-overexpression. The S-nitrosylation of HA2 at Cys206 suppressed its interaction with 14-3-3 protein 1 (TFT1), culminating in the inhibition of its enzymatic activity and saline-alkali tolerance. Under physiological status, melatonin and NO jointly act as a redox switch of HA2 to regulate root H+ and Na+ efflux to affect saline-alkali tolerance. Thus, the COMT-, GSNOR-, and HA2-transgenic grafting significantly improved tomato productivity in natural saline-alkali soil. Together, this study unravels the molecular basis of the melatonin-NO-HA2 module and provides effective solution to agricultural applications.
Identifying internal distributions and multi-scenario simulation of ecosystem service value in Liaohe basin based on Geodetector and PLUS model
Authors: Jia Changgeng , Wei Chaoxiang , Luo Kunyu , Li Sihui , Fan Yu
Published: August 2023

Ecosystem services value (ESV) can assess the level of basin ecological restoration and provide a basis for ecological management decision-making. This study object selects Liaohe River Basin (LHB), a typical basin in Northeast China. The ecosystem service value variation caused by changes in land use cover and the spatial distribution characteristics was evaluated by employing the benefit transfer method, which is based on data sets for land use over 2000–2020. Meanwhile, geographical detector was employed to investigate the impacts and interactions of various factors driving the ESV, and predicted future changes in land and ESV by PLUS model. The results showed the following: 1) LHB land transformations mainly concentrated in the transformation between grassland, farmland and forestland. ESV in LHB decreased and then increased between 2000 and 2020 (1224 billion-928 billion-1238 billion), 2) Ecosystem service value exhibited a strong positive spatial autocorrelation, high ESV was mainly distributed in the eastern and western regions of LHB, and low ESV in the central region. 3) The variation in ecosystem service value mainly arises from the human activity intensity index of human factors. 4) In the future, the ecological protection priority scenario can improve the ESV in LHB, and the natural development priority and economic development priority scenario is not conducive to the improvement of ESV. The results show that the ecological restoration effect of the LHB is obvious with the ecosystem service value is significantly improved. In the future, attention should be paid to control human activities and strengthen ecological protection in ESV hotspots.
Genetic structure of brine shrimp Artemia in central-west China: cumulative effects of ancient geological events, climatic changes and recent human activities
Authors: Li Ke , Zhang Rui , Sui Liying , Zhang Chi , Han Xuekai
Published: August 2023

Brine shrimp Artemia is the crucial live food in fish and crustacean larviculture. With the decrease of Artemia resources and the increase in aquaculture demand, it is necessary to conduct Artemia population genetics and to manage this important resource efficiently. In this study, the genetic diversity and distribution pattern of Artemia populations originated from ten inland salt lakes in central-west China were studied using a large number of single nucleotide polymorphisms (SNPs) obtained by high-throughput sequencing. The results showed that Tibetan populations had the highest level of genetic diversity, while Shanxi population had the lowest value. Genetic structure and principal component analysis further revealed these populations can be classified into four geographically and genetically distinct groups, and Tibetan populations were further divided into two subgroups and showed a trend of higher in the west and lower in the east at the level of genetic diversity. In addition, a certain amount of gene flow was observed among these 10 populations, and A. sinica had a unidirectional gene flow to all populations in the eastern Nagri region. Finally, species distribution models indicated that Bio1, Bio4, and Bio12 were the main environmental factors affecting the distribution of Artemia, and climate fluctuations had a strong influence on the distribution of Artemia. The findings revealed Tibetan populations will be further reduced in the future, and it is necessary to adopt a series of measures to strengthen Artemia protection and promote rational exploitation and utilization of this natural resources. This study further improves our understanding of the genetic structure of Artemia in central-west China, and provides certain guidance for the protection of Artemia germplasm resources.
Exhaustion, rather than lack of infiltration and persistence, of CAR-T cells hampers the efficacy of CAR-T therapy in an orthotopic PDAC xenograft model
Authors: Takeuchi Yuta , Wang Yizheng , Sasaki Katsunori , Sato Osamu , Tsuchikawa Takahiro , Wang Linan , Amaishi Yasunori , Okamoto Sachiko , Mineno Junichi , Hirokawa Yoshifumi , Hatanaka Kanako C. , Hatanaka Yutaka , Kato Takuma , Shiku Hiroshi , Hirano Satoshi
Published: August 2023

Background The impressive success of chimeric antigen receptor (CAR)-T therapy in the treatment of hematologic tumors is leading researchers/clinicians to broaden the possible application of this approach to patients with solid tumors, especially patients with pancreatic ductal adenocarcinoma (PDAC). However, CAR-T cell therapy faces disappointing clinical results in solid tumors due to hurdles unique to solid, but not hematologic, tumors, which include restricted trafficking and limited infiltration into tumors, non-durable persistence, and T cell exhaustion. Since the tumor microenvironment composition varies between tumor type meaning CAR-T cells again face a unique set of challenges in each solid tumor, the major hurdle imposed by PDAC on CAR-T cell therapy remains elusive.Methods In this study, we used immunodeficient NOD/Shi-scid, IL-2RγKO Jic mice orthotopically transplanted with human pancreatic tumor cell line, BxPC-3, and transferred with CAR-T cells specific to carcinoembryonic antigen (CEA), a model that allows analysis of quantitative, spatial and functional dynamics of CAR-T cells in tumor tissues unique to PDAC.Results CAR-T cells suppressed tumor growth of orthotopic human PDAC tumors, but only within a limited time window. Contrary to previous studies that demonstrated a limited persistency and infiltration of CAR-T cells in many solid tumors, they persist and accumulated in PDAC tumor tissues, but CAR-T cells become progressively lost ability to control tumor growth. Ex vivo analysis revealed that CAR-T cells that had been recovered at different time points from mice bearing an orthotopic PDAC tumor exhibited a gradual loss of tumor reactivity. This loss of tumor reactivity of CAR-T cells was associated with the increased expression of AMP-activated protein kinase and Mitofusin1.Conclusions The present results demonstrate the potential effectiveness of CAR-T cells in targeting CEA for the treatment of PDAC. However, optimization of CAR-T cells, especially in the areas of resistance to exhaustion is required.
Realization of Collimated Specific Profiles in Rotation-Symmetrical Beam Shaping System with Divergent Light Source
Authors: Tsai Cheng-Mu , Yu Tzu-Chen , Han Pin , Fang Yi-Chin
Published: August 2023

A simple numerical method is proposed for the design of two freeform surfaces, each comprising multiple segmented refractive planes, for generating a collimated beam with a specific irradiance profile in a beam shaping system with a divergent light source. However, in real-world manufacturing, this performance improvement is obtained at the expense of a greater cost and complexity. Accordingly, a second algorithm is proposed which maximizes the number of rays passing through the central regions of the refractive planes in the second freeform surface and hence minimizes the total number of segments required to achieve the same beam shaping performance. The feasibility of the proposed method is demonstrated through the design of two freeform lenses for generating collimated output beams with ring- and triangle-like irradiance profiles, respectively. The experimental results show that the beam profiles are in close agreement with the desired irradiance distributions. In general, the results indicate that the proposed method provides a versatile and efficient approach for achieving the desired collimated profile in beam forming systems with a divergent light source.
A Standardized Rat Model to Study Percutaneous/permucosal Osseointegrated Implants Peri-implantitis
Authors: Liu Xingchen , Deng Shudan , Li Xiyan , Liu Haiwen , Li Zhixin , Wu You , Luo Pu , Zhong Xinyi , Huang Ruoxuan , Liu Runheng , Wu Xiayi , Huang Baoxin , Chen Zetao , Chen Zhuofan , Chen Shoucheng
Published: August 2023

Background:Percutaneous/permucosal osseointegrated implants(POI) are increasingly utilized in clinical practices. However, POI peri-implantitis because of bacterial colonization remains an unsolved problem. With the high incidence rate, distinctive implant characteristic and unique infection pattern, POI peri-implantitis requires a specially designed implant animal model for the researches on the pathogenesis and treatments. Although POI peri-implantitis animal models in forelimb or oral cavity have been utilized in several studies, their high variability in terms of implant site selection, implant design and surgical procedures,etc., have led to unnecessary tissue damage and less effectivity. Herein, a quantitative-analysis-based standardized rat model for POI related research was proposed.Methods:The hard and soft tissue anatomical structures in region anterior to maxillary molar of rat were systematically evaluated by micro-computed tomography (micro-CT) and vascular perfusion to obtain the best surgical site. We then managed to standardize the model by controlling the age, weight, gender of rats and designing implant based on the quantitative-analysis of available volume of bone and soft tissue. Besides,customized instruments andstep-by-step surgical procedures were developed to avoid damage important structures and reduce the variations.Finally, comprehensive assessments including the expression of biomarkers, micro-CT, and histological images were conducted to verify the model.Results:After dissecting the anatomic structures of rat maxilla, we found that placing the implant anterior to the first molar could reduce experimental period and improve animal welfare. We standardized the model by including Sprague-Dawley male rats weighing 450–500g and aged 12–13 weeks. The customized implant size, shape, and a series of matched surgical instruments were appropriately designed. A clear,step by step, surgical process was established. The aforementioned designs ensured the success rate, stability, and replicability of the model.Each validation method confirmed the successful construction of the model.Conclusions:This study proposed a quantitative-analysis-based standardized POI peri-implantitis rat model with improved animal welfare and reliable procedures. This model could provide efficientin vivoinsights to study the pathogenesis and treatmentsof POI peri-implantitis and preliminary screening data for further large animal and clinical trials.
Preliminary utility of group acceptance and commitment therapy for patients with intractable chronic pain presenting to a multidisciplinary pain center in Japan: a single-arm pre- and post-comparative study
Authors: Sakai Mie , Kondo Masaki , Muto Takashi , Sugiura Takeshi , Akechi Tatsuo
Published: August 2023

Background: Multidisciplinary treatments, including psychological approaches such as Acceptance and Commitment Therapy (ACT), are useful for treating chronic pain. However, the few studies investigating the use of ACT on patients with chronic pain in Japan have been limited to case studies and case series. There is a need to develop a Japanese version of a standardized intervention program to expand the use of ACT for patients with chronic pain in Japan. Therefore, the present study examined the preliminary utility of an ACT program for Japanese patients with chronic pain with the ultimate aim of developing a standardized intervention program.
Methods: This was a single-arm, pre-test, and post-test comparative study including 23 patients with chronic pain. Patients attended seven weekly group therapy sessions. Psychological scales were administered before and after the intervention, and results were compared using t-tests.
Results: Following the intervention, participants displayed more positive attitudes towards pain (Chronic Pain Acceptance and Action Questionnaire-pain willingness, d = 0.83), pain catastrophic thinking (Pain Catastrophizing Scale, d = 0.71), receptive attitudes towards pain (Chronic Pain Acceptance and Action Questionnaire-total, d = 0.60), and the degree of pain interference (Brief Pain Inventory-interference, d = 0.55). The intervention had a moderate effect on pain intensity (Brief Pain Inventory-intensity, d = 0.43) and progress along the value (Valuing Questionnaire, d= 0.67).
Conclusions: The preliminary value of the program was demonstrated by its significant effect on pain acceptance. Further efficacy studies comparing groups are required.
Identification of CT-based non-invasive Radiographic Biomarkers for Overall Survival Stratification in Oral Cavity Squamous Cell Carcinoma
Authors: Ling Xiao , Alexander Gregory S. , Molitoris Jason , Choi Jinhyuk , Schumaker Lisa , Mehra Ranee , Gaykalova Daria A. , Ren Lei
Published: August 2023

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma OSCC survival prediction by identifying Computed Tomography (CT)-based biomarkers for improved prognosis. A retrospective analysis was conducted on data from 149 OSCC patients, including radiomics and clinical. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as smoking and alcohol usage, as survival biomarkers. The GNS group with values above 14 showed a hazard ratio of 0.12 and a 3-year survival rate of about 90%. Conversely, the GNS group with values less than or equal to 14 had a 49% survival rate. For normalized HLE, the high-end group (HLE > -0.415) had a hazard ratio of 2.41, resulting in a 3-year survival rate of 70%, while the low-end group (HLE <= -0.415) had a 36% survival rate. These findings contribute to our knowledge of how radiomics can be used to anticipate the outcome and tailor treatment plans from people with OSCC.
Assessing the impact of mining exploration infrastructure on ground-dwelling arthropod communities using DNA metabarcoding and habitat characteristics.
Authors: Fernandes Kristen , Clark-Ioannou Sophia , Saunders Benjamin J , Majer Jonathan , Bateman Philip W , Bunce Michael , Nevill Paul
Published: August 2023

For most mining projects, regular monitoring of environmental impacts is typically measured solely for the main operation footprint and not the supporting network of exploration infrastructure. Such infrastructure includes exploration tracks, roads and drill pads, where localised areas are cleared of native vegetation, and the surrounding habitat is undisturbed. Here we use DNA metabarcoding to study the impacts of mining exploration infrastructure on the ground-dwelling arthropod communities found on Banded Ironstone Formations (BIFs) in the Midwest region of Western Australia. Further, we examine whether two indicator species groups, Formicidae and Collembola, reflect the patterns in overall arthropod communities. The study was conducted at three mine sites, each with three infrastructure types: maintained tracks, unmaintained tracks, and drill pads. We collected ground-dwelling arthropods and recorded habitat characteristics (e.g. total vegetation cover, bare ground cover) along transects extending 100 m away from the disturbance into remnant vegetation. We found that all three infrastructure types impacted the habitat characteristics similarly, with physical changes in habitat extending into the remnant vegetation. However, among all three groups of arthropods (overall arthropods, Formicidae and Collembola), we observed a clear distinction between each exploration infrastructure type at the three sites, indicating a disturbance effect extending more than 100 m into remnant vegetation. We found that Formicidae communities reflected the changes in overall arthropod communities better than Collembola. Our results demonstrate the utility of DNA metabarcoding for documenting fine-scale impacts on arthropod communities and highlight the need to consider different types of disturbances associated with mining activity.
Navigating Through Complexity: Profiling the main threats to Sustainable Tropical Wetlands Management and its Implications to livelihoods welfare and ecosystem governance: A Case Study of Mityana District, Uganda
Authors: Matovu Baker , Sarfo Isaac , Bbira Yasin , Yeboah Emmanuel , Muhoozi Yosia
Published: August 2023

Wetlands are crucial ecosystems that promote sustainable livelihood and biodiversity conservation, especially in tropical regions. However, recent studies have reported increasing threats to wetlands both environmental and human which threaten the provision and acquisition of several wetland benefits. Though there is recognition of the value of wetlands, in most local communities, there is limited knowledge and research on the benefits of wetlands and the level of threat thus affecting wetland governance. This research addresses this gap by conducting participatory research to create a baseline inventory that identifies the main wetlands and threats to inform policy. The study was conducted in 14 sub-counties and a sample of 105 wetlands along the wetlands of Lake Wamala and River Mayanja wetlands system in Mityana District was captured. The field data was collected from 150 respondents. Study findings found that there is an increasing human threat to wetlands especially in the River Mayanja seasonal wetlands and the level of damage/threat on Lake Wamala wetlands. Respondents further reported an increasing threat of environmental drivers such as climate change. Since the level of damage to wetlands in Mityana especially the permanent wetlands is relatively low, we recommend a focus on capacity building, development of wetlands action plans, increased support to local wetland authorities, and a system thinking approach in wetland threat identification and management.