bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of Pests, Natural Enemies and Pollinators of Lycopersicon esculentum Mill and Correlation with Weather Parameters
Authors: Goudia N. , Jena M. K. , Singh R. R.
Published: April 2023

The experiment was carried out at K.V.K. Instructional Farm located near College of Agriculture, Odisha University of Agriculture and Technology (O.U.A.T.), Bhawanipatna, Kalahandi, during the cropping season 2020–21. The most significant pests found in Lycopersicon esculentum Mill were tomato fruit worm, serpentine leaf miner, and whitefly, while flea beetle was of minor importance.The population of whitefly had significant negative correlation with evening and mean relative humidity (RH). The population of leaf miner had significant positive correlation with maximum, minimum and mean temperature but significant negative correlation with mean RH. There was a significant positive correlation of flea beetle population with minimum temperature. The tomato fruit borer population had significant positive correlation with maximum, minimum and mean temperature but significant negative correlation with morning and mean RH. The natural enemies, lady bird beetles, spiders, praying mantis, rove beetle, red ant, dragonfly (red body) and damselflies (blue, brick red and black body) were found in the plots. The population of spider had significant negative correlation with maximum, minimum and mean temperature but significant positive correlation with bright sunshine hours (BSH). The population of spider had significant negative correlation with evening RH but significant positive correlation with BSH. There was a significant positive correlation of red ant population with BSH. The population of rove beetle had significant positive correlation with maximum, minimum and mean temperature. The pollinators recorded from experimental field were honey bee and carpenter bee. Of which, carpenter bee was the most frequent floral visitor and considered the main pollinator of tomato. The pollinators appeared in higher numbers during the blooming period and was the dominant species found in the field. There was a significant negative correlation of population of carpenter bee with maximum, minimum and mean temperature. The population of honey bee had significant negative correlation with evening RH.
Impact of Cluster Frontline Demonstrations on Yield of Chickpea (Cicer arietinum L.) in Prakasam District of Andhara Pradesh, India
Authors: Ramesh G. , Durgaprasad N. V. V. S. , Jahnavi M. , Chowdary L. Rajesh
Published: April 2023

The Cluster Front Line Demonstrations (CFLDs) offer a unique approach to establish a direct interface between farmers and researchers, where the latter are involved in planning, executing, and monitoring the demonstrations. The objective of the current study was to evaluate the impact of front line demonstrations conducted for chickpea crop in the Prakasam district of Andhra Pradesh state. Chickpea (Cicer arietinum L.) is a highly nutritious legume crop that is widely recognized as both a health food and a high-return crop. The front line demonstrations were conducted at the farmers’ fields to showcase the production potential and economic benefits of improved technologies. The findings revealed that the implementation of improved cultivation practices recommended under CFLDs, such as the use of recommended varieties, appropriate seed rate, timely sowing, and plant protection technology, resulted in a significant increase in gram crop yield compared to the check plots. The adoption of improved technologies led to higher yields, recording chickpea yields of 21.25, 21.75, and 19.50 q/ha during 2018-19, 2019-20, and 2020-21, respectively, which were 13.35%, 24.37%, and 22.22% higher than the prevailing farmer's practice. The average seed yield under improved practice (IP) was 20.83 q/ha, which was 15.48% higher than the farmer's practice (FP). The technology gap and extension gap ranged from 3.25 to 5.50 q/ha and 1.50 to 4.25 q/ha, respectively. The technology index value varied from 13.0% to 22.0% during the study period. The benefit-cost (B: C) ratio ranged from 2.23 to 2.84 under demonstration, while it was 2.15 to 2.57 under control plots. The average B: C ratio under IP (2.53) was 39.89% higher than that under FP.
3G Cutting: An Innovative Tool in Cucurbitaceous Crops to Boost the Production and Doubling the Income of Small Farmers in a Per Unit Area
Authors: Verma Aniket Kumar , Goutam Etalesh , Gangwar Vaishali , Singh Pranjal , Prajapati Jaswant , Singh Devraj , Mishra A. C. , Patel Vikas , Singh Ritesh
Published: April 2023

3G cutting is one of the most popular and successful inter-culture operations in cucurbitaceous crops like; bottle gourd, cucumber, pumpkin, sponge gourd, bitter gourd, etc. as well as in plants like tomato, eggplant, chilli, and lady’s finger for a small patch of land. Low fruit set is an emerging constraint in cucurbits, and when it does, extremely small-sized fruits develop and degrade the mother plant. This is the main problem that farmers are currently facing. This problem arises due to a rapid decrease in beneficial insects and other pollinators as a result of the haphazard use of foliar fertilizers and chemical pesticides. 3G cutting is a scientific process to get higher production from plants by increasing the number of female flowers in the plant by adopting practices like trimming and pruning of 1st and 2nd generation branches.  Generally, 1G and 2G branches have more no. of male flowers than female (approximately in the ratio of 14:1) whereas this ratio is reduced to 1:2 in 3G branches. We are all known that fruits develop from female flowers, while one male flower can pollinate several female flowers. However, this does not imply that there is no need for male flowers. Male flowers are necessary for pollination. Thus, 3G cutting is the finest scientific practice for farmers to maximize the number of female flowers and fruit yield.
The Experience of Infertility: A Review of Recent Literature on Male Infertility Due to Post Testicular Disorders
Authors: Abdalla Rania Abdeen Hussin
Published: April 2023

Infertility is usually well-defined as the inability of a couple to conceive even after one year of unprotected, frequent sexual intercourse [1,2]. At least 180 million people worldwide and about 15% of all couples in the US are affected by it [3,4]. Male infertility is defined as the inability of a male to successfully carry a fertile female to term, also for at least one year of unprotected sexual activity. About 20% of all cases of infertility are solely the male's fault, and another 30% to 40% have the male as a contributing factor [5]. Due to the frequent coexistence of male and female causes of infertility, it is crucial that both partners undergo infertility testing and receive joint management. A total of 50% of all cases of infertility are significantly attributed to the male factor [6-8]. Even though clinical emphasis still dominates research, more studies are now situating infertility within broader social contexts and social scientific frameworks. Methodological issues persist, but there have also been significant advances. In the social scientific study of infertility, we identify two active research traditions. In order to enhance service delivery and determine the need for psychological counseling, one tradition studies clinic patients primarily using quantitative techniques. The other tradition uses primarily qualitative research to capture the experiences of infertile people in a sociocultural context. We conclude that more attention is now being paid to the ways in which the experience of infertility is shaped by social context. We call for continued progress in the development of a distinctly sociological approach to infertility and for the continued integration of the two research traditions identified here.
Herbicide Management for Sustainable Sugar Cane (Saccharum officinarum l.) Production in Sudan
Authors: Alama I. E. Abu , Yagoub S. O. , Hassan M. M. , Abdelhalim M. , Khalil N. A. , Hdad M. A.
Published: April 2023

Field investigations were carried out during 2018/19 at Sugarcane Research Center Farm El Guneid, Sudan, in two sites, to evaluate the effect of the combination of chemical herbicides, Ametryne (3.8 L/ha) + Atrazine (3.8 L/ha), Atrazine (3.0 L/ha) + Pendimethalin (2.9 L/ha) and Metribuzin (5.21 L/ha) + Pendimethalin (3.57 L/ha), on common weed control, sugar cane growth, yield and quality. Experimental design was a randomized complete block (RCBD) with three replications. Results revealed that the combination of Metribuzin (5.21 L/ha) + Pendimethalin (3.57 L/ha) recorded the best results in weed control efficiency percent (WCE%) for both grass and broadleaved weeds in sugarcane crop compared to the other treatmentsand the control in the two sites. On the other hand, significant difference of means between treatments was observed in growth parameters and yield of sugar cane at 3, 6 and 9-month ages. Among all treatments the combination of Metribuzin (5.21 L/ha)+Pendimethalin (3.57 L/ha) showed the best results, irrespective to parameters compared to the other treatments and the control in the two sites. The mixture of Metribuzin+pendimethalin sustained the highest WCE% for both, grass and broadleaved weeds in addition to increased cane yield and yield component compared to other treatments and the corresponding control. Based on this study, it can be concluded that the herbicide combination provided effective weed control and promoted sugarcane quality and yield. Therefore, the use of herbicides not only increases the net income of farmers, but also demise weeds seed bank.
Noninductive Control of Permanent Magnet Synchronous Motor Based on Improved Synovial Observer
Authors: Haichao Liu , Peng Sun
Published: April 2023

In the non-inductive control of permanent magnet synchronous motor, the rotor position information of the motor is usually estimated by the synovial film observer. Synovial observer has the advantages of simple control structure and short response time. The switch function of the control process of the synovial observer is usually the sign function. The back electromotive force signal is extracted by the filter, and then the rotor position information is estimated by the inverse tangent method. However, the traditional switching process of sign function contains a large number of high order harmonics, which will cause the problems of phase difference and amplitude attenuation after the signal is filtered by the filter, and the estimation error of arctangent method is large. Based on the above problems, the traditional switching function is improved in this paper. Continuous sigmoid function is used as the switching function, which can effectively solve the problem of excessive vibration during the operation of the motor. In addition, phase-locked loop technology is introduced to replace the traditional inverse tangential method for rotor position estimation, which further improves the estimation accuracy of the system.
Optimization Analysis of Hardness Test for Powdered Pentaclethra macrophylla Pod /Bio-Epoxy Resin Based Brake Pad Composite Using Central Composite Design
Authors: Iloabachie I. C. C. , Atuanya C. U. , Ogbu C. C.
Published: April 2023

This work examined the optimization of hardness test for Powdered Pentaclethra macrophylla  Pod /Bio-Epoxy Resin Based Brake Pad Composite Using Central Composite Design. The Pentaclethra macrophylla  pod was manually cleaned and sun-dried for about three hours per day for three days. The sun-dried Pentaclethra macrophylla pod was later ovum dried at a temperature of about 110oC for three hours to achieve a constant weight and subsequently allowed to cool to room temperature. The ovum-dried Pentaclethra macrophylla pod was crushed to powder form using locally fabricated grinding machine and sieved. Part of the sieved powdered pod was carbonized in a heat treatment furnace at a temperature of about 950oC. Pre-impregnated process was used to prepare the brake pad composite samples. The weights of the powdered Pentaclethra macrophylla  pods and bio-epoxy resin were varied while those of the lubricant, abrasives, friction modifier, catalyst and accelerator were kept constant The weights of the reinforcement i.e. powdered Pentaclethra macrophylla  pods were varied between 10 wt. % and 50 wt. % at an interval of 10 wt. %. The formulation was poured into a wooden mould 50 mm × 50 mm × 8 mm placed in a hot platen press at temperature of about 180oC, a moulding pressure of 15MPa and a curing time of 5 minutes. Post-heat treatment of the composites was performed in a hot air oven for a period of 4 hours at 180 °C. The produced brake pads were evaluated for hardness in accordance to ASTM D785 standard using Rockwell Scale K hardness testing machine. The results of the test showed that 150μm particle size reinforced brake pad sample had higher hardness values of 105.7 and 106.4 at 20wt. % and 30wt. % respectively. This result was also confirmed by the Central composite design (CCD) where maximum hardness values of 107.31 and 107.63 were obtained at 20wt. % and 30wt. % respectively.
Optimizing Crop Yields through Machine Learning-Based Prediction
Authors: Harshith Maddila , Sahu Ayushi , Indrakanti Sanju , Reddy R. Kameshwar , Bhutada Sunil
Published: April 2023

The application of machine learning techniques in agriculture, particularly in harvest forecasting, is gaining traction as a means of addressing this issue. The major project, "Optimizing Crop Yields through Machine Learning-Based Prediction," takes a comprehensive approach to this issue by considering a variety of parameters, including temperature, humidity, rainfall, and soil nutrient levels, to Figure out which crop is best to grow in those conditions. Naive Bayes, Random Forest, Support Vector Machines, Decision Trees, K-Nearest Neighbours, and Bagging, as well as feature selection methods like Synthetic Minority Oversampling Technique, Majority Weighted Minority Oversampling Technique, Random Over-Sampling Examples, and Recursive Feature Elimination, are used to accomplish this. High precision rates and improved forecast outcomes are the goals of these methods. Using machine learning techniques in crop forecasts, farmers can gain useful insights and make decisions based on data that increase crop production and overall agricultural productivity. This work demonstrates the potential of machine learning to address issues in agriculture and influence the sector's future.
Visual Multifunctional Aggregation‐Induced Emission‐Based Bacterial Cellulose for Killing of Multidrug‐Resistant Bacteria
Authors: Shen Zipeng , Zhu Wei , Huang Yajia , Zhang Jiangjiang , Wu Yifan , Pan Yinzhen , Yang Guang , Wang Dong , Li Ying , Tang Ben Zhong
Published: April 2023

Multidrug‐resistant (MDR) bacteria‐related wound infections are a thorny issue. It is urgent to develop new antibacterial wound dressings that can not only prevent wounds from MDR bacteria infection but also promote wound healing. Herein, an aggregation‐induced emission (AIE) molecule BITT‐composited bacterial cellulose (BC) is presented as wound dressings. BC‐BITT composites have good transparency, making it easy to monitor the wound healing process through the composite membrane. The BC‐BITT composites retain the advantages of biocompatible BC, and display photodynamic and photothermal synergistic antibacterial effects under irradiation of a 660 nm laser. Furthermore, the BC‐BITT composites show excellent wound healing performance in a mouse full‐thickness skin wound model infected by MDR bacteria, simultaneously with negligible toxicity. This work paves a way for treating clinically troublesome wound infections.
A Multifunctional Nanocarrier System for Highly Efficient and Targeted Delivery of Ketamine to NMDAR Sites for Improved Treatment of Depression
Authors: Ge Jing , Tan Ronghua , Gao Qian , Li Rui , Xu Pengxin , Song Hang , Wang Shenqi , Wan Ying , Zhou Lei
Published: April 2023

Ketamine (KA), commonly used as an anesthetic, is now widely studied as an antidepressant for the treatment of depression. However, due to its side effects, such as addiction and cognitive impairment, the dosage and frequency of (S)‐ketamine approved by the FDA for the treatment of refractory depression is very low, which limits its efficacy. Here, a new multifunctional nanocarrier system (AC‐RM@HA‐MS) with specific targeting capabilities is developed to improve the efficacy of KA treatment. KA‐loaded NPs (AC‐RM@HA‐MS‐KA) are constructed with a multilayer core–shell structure. KA‐loaded mesoporous silica NPs are prepared, conjugated with hyaluronic acid (HA) as pore gatekeepers, and sheathed with an RBC‐membrane (RM) for camouflage. Finally, the surface is tagged with bifunctional peptides (Ang‐2‐Con‐G, AC) to achieve specific targeting. One peptide (Ang‐2) is acted as a guide to facilitate the crossing of the blood–brain barrier (BBB), while the other (Con‐G) is functioned as a ligand for the targeted delivery of KA to the N‐methyl‐D‐aspartate receptor sites. Animal experiments reveal that AC‐RM@HA‐MS‐KA NPs effectively cross the BBB and directionally accumulate in the curing areas, thereby alleviating the depressive symptoms and improving the cognitive functions of depressed mice. After treatment, the depressed mice almost completely return to normal without obvious symptoms of addiction.
ROS Scavenging Nanozyme Modulates Immunosuppression for Sensitized Cancer Immunotherapy
Authors: Mo Wenjing , Liu Shujie , Zhao Xiaozhi , Wei Fayun , Li Yuhang , Sheng Xinan , Cao Wenmin , Ding Meng , Zhang Wenlong , Chen Xiaoqing , Meng Longxiyu , Yao Sheng , Diao Wenli , Wei Hui , Guo Hongqian
Published: April 2023

Myeloid‐derived suppressor cells (MDSCs) and tumor‐associated macrophages (TAMs), two immunosuppressive myeloid components within the tumor microenvironment (TME), represent fundamental barriers in cancer immunotherapy, whereas current nanomedicines rarely exert dual modulatory roles on these cell types simultaneously. Reactive oxygen species (ROS) not only mediates MDSC‐induced immunosuppression but also triggers differentiation and polarization of M2‐TAMs. Herein, an ROS scavenging nanozyme, Zr‐CeO, with enhanced superoxide dismutase‐ and catalase‐like activities for renal tumor growth inhibition is reported. Mechanistically, intracellular ROS scavenging by Zr‐CeO significantly attenuates MDSC immunosuppression via dampening the unfolded protein response, hinders M2‐TAM polarization through the ERK and STAT3 pathways, but barely affects neoplastic cells and cancer‐associated fibroblasts. Furthermore, Zr‐CeO enhances the antitumor effect of PD‐1 inhibition in murine renal and breast tumor models, accompanied with substantially decreased MDSC recruitment and reprogrammed phenotype of TAMs in the tumor mass. Upon cell isolation, reversed immunosuppressive phenotypes of MDSCs and TAMs are identified. In addition, Zr‐CeO alone or combination therapy enhances T lymphocyte infiltration and IFN‐γ production within the TME. Collectively, a promising strategy to impair the quantity and function of immunosuppressive myeloid cells and sensitize immunotherapy in both renal and breast cancers is provided.
Engineered Curli Nanofilaments as a Self‐Adjuvanted Antigen Delivery Platform
Authors: Lamontagne Félix , Arpin Dominic , Côté‐Cyr Mélanie , Khatri Vinay , St‐Louis Philippe , Gauthier Laurie , Archambault Denis , Bourgault Steve
Published: April 2023

Proteinaceous nanoparticles constitute efficient antigen delivery systems in vaccine formulations due to their size and repetitive nature that mimic most invading pathogens and promote immune activation. Nonetheless, the coadministration of an adjuvant with subunit nanovaccines is usually required to induce a robust, long‐lasting, and protective immune response. Herein, the protein Curli‐specific gene A (CsgA), which is known to self‐assemble into nanofilaments contributing to bacterial biofilm, is exploited to engineer an intrinsically immunostimulatory antigen delivery platform. Three repeats of the M2e antigenic sequence from the influenza A virus matrix 2 protein are merged to the N‐terminal domain of engineered CsgA proteins. These chimeric 3M2e‐CsgA spontaneously self‐assemble into antigen‐displaying cross‐β‐sheet nanofilaments that activate the heterodimeric toll‐like receptors 2 and 1. The resulting nanofilaments are avidly internalized by antigen‐presenting cells and stimulate the maturation of dendritic cells. Without the need of any additional adjuvants, both assemblies show robust humoral and cellular immune responses, which translate into complete protection against a lethal experimental infection with the H1N1 influenza virus. Notably, these CsgA‐based nanovaccines induce neither overt systemic inflammation, nor reactogenicity, upon mice inoculation. These results highlight the potential of engineered CsgA nanostructures as self‐adjuvanted, safe, and versatile antigen delivery systems to fight infectious diseases.
Understanding the Interfacial Reactions and Band Alignment for Efficient and Stable Perovskite Solar Cells Built on Metal Substrates with Reduced Upscaling Losses
Authors: Li Tieqiang , Mao Kaitian , Meng Hongguang , Zhu Zhengjie , Peng Wei , Yuan Shaojie , Xu Jiahang , Feng Xingyu , Xu Zijian , Xu Jixian
Published: April 2023

Conventional perovskite solar cells (PSC) built on transparent conductive oxide (TCO) glass face a fundamental challenge to retain fill factor (FF) for large‐area upscaling due to series resistance loss. Building a perovskite solar cell on metal has the potential to reduce this FF loss and is promising for flexible applications. However, their efficiency and stability lag far behind their TCO counterparts. Herein, findings on the complex chemical reactions and degradation‐promoting processes at different perovskite/metal (Cu, Au, Ag, and Mo) interfaces, which are closely linked with the inherent stability; and the interlayer engineering for perovskite/metal interface's band alignment, which plays an essential role in achieving high efficiency, are reported. Leveraging these findings, 21% power conversion efficiency (PCE) is achieved for 1 cm2 perovskite solar cells using a p–i–n top‐illumination structure on a molybdenum substrate, the highest reported for a PSC built on metal. Notably, the FF and PCE losses due to area upscaling are remarkably reduced by one order of magnitude relative to the counterparts on conventional TCO glass, highlighting an alternative pathway for PSC upscaling and module design.
Precise Control of Single‐Crystal Perovskite Nanolasers
Authors: Zhuge Minghua , Yin Jun , Liu Yilin , Wang Yuhan , Li Ziyu , Xiao Shumin , Yu Shaohua , Song Qinghai
Published: April 2023

Efficient control of integrated light sources is crucial to advancing practical applications of nanophotonics. Despite the success of microlasers, their sophisticated nanostructures are not applicable in nanolasers. The situation for bottom‐up‐synthesized nanolasers becomes more challenging due to the constraints of fixed cavity shapes and fragile material stability. Here, the physics of exceptional points (EPs) is employed, and a strategy is demonstrated to precisely tune the lasing actions in lead halide perovskite nanorods. By placing a nanoparticle to the boundary of a square nanocavity, it is shown that EPs regularly and controllably emerge as a function of the nanoparticle position. Consequently, both the internal lasing actions and their far‐field radiation can be completely reversed with a tiny displacement of <100 nm. The new strategy for controlling lasing actions in nanocavities is confirmed with numerical simulations and lasing experiments. This research can also bring new avenues for ultrasensitive position sensing.
Soft Functionally Gradient Materials and Structures – Natural and Manmade: A Review
Authors: Pragya Akanksha , Ghosh Tushar K.
Published: April 2023

Functionally gradient materials (FGM) have gradual variations in their properties along one or more dimensions due to local compositional or structural distinctions by design. Traditionally, hard materials (e.g., metals, ceramics) are used to design and fabricate FGMs; however, there is increasing interest in polymer‐based soft and compliant FGMs mainly because of their potential application in the human environment. Soft FGMs are ideally suitable to manage interfacial problems in dissimilar materials used in many emerging devices and systems for human interaction, such as soft robotics and electronic textiles and beyond. Soft systems are ubiquitous in everyday lives; they are resilient and can easily deform, absorb energy, and adapt to changing environments. Here, the basic design and functional principles of biological FGMs and their manmade counterparts are discussed using representative examples. The remarkable multifunctional properties of natural FGMs resulting from their sophisticated hierarchical structures, built from a relatively limited choice of materials, offer a rich source of new design paradigms and manufacturing strategies for manmade materials and systems for emerging technological needs. Finally, the challenges and potential pathways are highlighted to leverage soft materials' facile processability and unique properties toward functional FGMs.
Mechanistic Insights into the Stepwise (4+2) Cycloaddition toward Chiral Fused Uracil Derivatives
Authors: Marcantonio Enrico , Zanardi Franca , Curti Claudio , Lombardo Marco
Published: April 2023

The mechanism of the previously reported stereoselective (4+2) cycloaddition of N‐protected 6‐methyluracil‐5‐carbaldehydes and (E)‐β‐nitrostyrenes catalyzed by Takemoto's tertiary amine/thiourea organocatalyst was explored, using density functional theory (DFT) calculations on a model representative reaction. The cyclization reaction, which afforded notable enantioenriched carbocycle‐fused uracils embedding three contiguous stereocenters, was here proven to be the result of a four‐step sequence comprising a key stereo‐defining Michael addition, followed by a completely diastereoselective intramolecular Henry reaction. Going beyond the hitherto reported activation modes, a complex and unprecedented network of hydrogen‐bonding interactions between the chiral catalyst and the reaction partners has been disclosed, in which the protonated tertiary amine and the thiourea moiety of the catalyst simultaneously activate both the electrophile and the nucleophile components. By applying the Energetic Span Model (ESM) to four competitive energetic profiles, we unveiled the most plausible reaction pathways best fitting the experimental data, with close correlation with the observed enantiomeric ratio of the product.

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Retromer Proteins Reduced in Down Syndrome and the Dp16 Model: Impact ofAPPDose and Preclinical Studies of a γ‐Secretase Modulator
Authors: Chen Xu‐Qiao , Sawa Mariko , Becker Ann , Karachentsev Dmitry , Zuo Xinxin , Rynearson Kevin D. , Tanzi Rudolph E. , Mobley William C.
Published: April 2023

Objective

The retromer complex plays an essential role in intracellular endosomal sorting. Deficits in the retromer complex are linked to enhanced Aβ production. The levels of the components of the retromer complex are reported to be downregulated in Alzheimer disease (AD). Down syndrome (DS) shares neuropathological features with AD. Recent evidence points to dysregulation of the retromer complex in DS. The mechanisms underlying retromer deficits in DS and AD are poorly understood.

Methods

We measured the levels of retromer components in the frontal cortex of cases of DS‐AD (AD in DS) as well as DS; the frontal cortex of a person partially trisomic (PT‐DS) for human chromosome 21 (HSA21), whose genome had only the normal 2 copies of theAPPgene, was also examined. We also analyzed these proteins in the Dp16 mouse model of DS. To further explore the molecular mechanism for changes in the retromer complex, we treated Dp16 mice with a γ‐secretase modulator (GSM; 776890), a treatment that reduces the levels of Aβ42 and Aβ40.

Results

We found VPS26A, VPS26B, and VPS29, but not VPS35, were significantly reduced in both DS and DS‐AD, but not in PT‐DS. Downregulation of VPS26A, VPS26B, and VPS29 was recapitulated in the brains of old Dp16 mice (at 16 months of age) and required increasedAppgene dose. Significantly, GSM treatment completely prevented reductions of the retromer complex.

Interpretation

Our studies point to increasedAPPgene dose as a compromising retromer function in DS and suggest a causal role for Aβ42 and Aβ40. ANN NEUROL 2023;94:245–258
Understanding aggression in autism across childhood: Comparisons with a non‐autistic sample
Authors: Quetsch Lauren B. , Brown Cynthia , Onovbiona Harlee , Bradley Rebecca , Aloia Lindsey , Kanne Stephen
Published: April 2023

As many as half of all autistic youth face challenges with aggression. And while research in this area is growing, the prevalence and characterization of aggressive behaviors across autistic development remains poorly understood. This lack of knowledge on the autistic experience is further clouded as aggression is rarely compared against non‐autistic youth samples. To address this gap in the literature, the present study compared autistic children (N = 450) to non‐autistic children (N = 432) on multiple caregiver‐report measures of aggressive behavior and associated constructs (i.e., anger, disruptive behavior) across key developmental periods (<6, 6–12, 13–17 years) via a cross‐sectional design. Outcomes indicated higher levels of verbal aggression and behavioral intensity for autistic youth across development. Further, autistic children under age 6 had more significant levels of physical aggression than non‐autistic peers; however, these levels became equal to non‐autistic peers as the youths aged. Implications for differences in the presence of aggressive behavior as well as possible treatment options for aggression are discussed.
High baseline tumor burden‐associated macrophages promote an immunosuppressive microenvironment and reduce the efficacy of immune checkpoint inhibitors through the IGFBP2‐STAT3‐PD‐L1 pathway
Authors: Wen Zhaowei , Sun Huiying , Zhang Zhihua , Zheng Yannan , Zheng Siting , Bin Jianping , Liao Yulin , Shi Min , Zhou Rui , Liao Wangjun
Published: April 2023

Background

Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor (ICI) treatment. This study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high (HTB) and low (LTB) tumor burden.

Methods

For in vivo studies, several mouse models of subcutaneous tumors were established, and transcriptome sequencing, immunohistochemistry, and flow cytometry assays were used to detect the immune status in these subcutaneous tumors. For in vitro experiments, co‐culture models, cytokine antibody arrays, western blotting, flow cytometry, and enzyme‐linked immunosorbent assays were used to explore the underlying molecular mechanisms

Results

We found that MC38 or B16 subcutaneous tumors from the HTB group did not show any response to anti‐programmed cell death protein‐1 (PD‐1) therapy. Through flow cytometry assays, we found that the infiltration with CD8+ T cells was significantly decreased whereas M2‐like macrophages were enriched in subcutaneous tumors of HTB groups compared with those of LTB group. These changes were not affected by the initial number of injected tumor cells or tumor age, nor could they be reversed by surgical tumor reduction. Intraperitoneal colony‐stimulating factor 1 receptor (CSF‐1R) inhibitor PLX3397 injection at different time points of tumor growth only had an effect when administered in the early tumor stage to maintain the “heat” of the tumor microenvironment during the process of tumor growth, thereby achieving a response to ICI treatment when the tumor grew to a large size. Mechanistically, we found that insulin‐like growth factor binding protein 2 (IGFBP2) expression levels were significantly elevated in HTB tumor tissues. IGFBP2 promoted the programmed death‐ligand 1 (PD‐L1) expression in M2‐like macrophages by activating signal transducer and activator of transcription 3 (STAT3), and PD‐L1+ M2‐like macrophages exerted an immunosuppressive effect by inhibiting the proliferation and activation of CD8+ T cells in a PD‐L1‐dependent fashion.

Conclusions

This study suggested that the low efficacy of ICI treatment in HTB tumors is mainly attributed to the intratumoral accumulation of PD‐L1+ M2‐like macrophages via the IGFBP2‐STAT3‐PD‐L1 signaling pathway and their substantial inhibitory effects on T cell proliferation and activation.
A modeling study to estimate prostate cancer‐specific mortality on active surveillance for men with favorable intermediate‐risk prostate cancer: Results from the SEARCH cohort
Authors: Kuhlmann Paige K. , Oyekunle Taofik , Klaassen Zachary , Amling Christopher L. , Aronson William J. , Cooperberg Matthew R. , Kane Christopher J. , Terris Martha K. , Freedland Stephen J.
Published: April 2023

Purpose

Limited data exist to help surgeons decide between active surveillance (AS) versus treatment for men with favorable intermediate risk (FIR) prostate cancer. To estimate the theoretical excess risk of prostate cancer‐specific mortality (PCSM) with AS versus radical prostatectomy (RP), we determined the risk of PCSM in FIR men undergoing RP and modeled the PCSM risk for AS using a range of increased PSCM scenarios ranging from 1.25x to 2x higher relative to RP.

Materials and Methods

We retrospectively reviewed data from men undergoing RP from 1988 to 2017 at 8 Veterans Affairs hospitals within the SEARCH cohort. Men with FIR PC were identified using the NCCN risk criteria. Risk of PCSM at 5, 10, and 15 years after RP was estimated. Using these estimates, PCSM was then modeled for AS using a range of increased risk of PCSM relative to RP ranging from 1.25x to 2x higher.

Results

For the 920 FIR men identified, 5‐, 10‐, and 15‐year survival estimates for PCSM after RP were 99.9%, 99.0%, and 97.8%, respectively. If the risk of PCSM on AS were 1.25–2x greater than RP, there would be 0.54%–2.17% excess risk of PCSM at 15 years.

Conclusions

The risk of death for FIR after RP is very low. Assuming even modestly increased PCSM with AS versus RP, the excess risk of death for AS in FIR is low even up to 15 years. These data support the consideration of AS as a relatively safe alternative to RP in FIR men, though prospective randomized trials are needed to validate these findings.
Therapeutic effects of anti‐GM2 CAR‐T cells expressing IL‐7 and CCL19 for GM2‐positive solid cancer in xenograft model
Authors: Sasaki Takahiro , Sakoda Yukimi , Adachi Keishi , Tokunaga Yoshihiro , Tamada Koji
Published: April 2023

Background

While chimeric antigen receptor (CAR)‐T cell therapy has demonstrated excellent efficacy in hematopoietic malignancies, its clinical application in solid cancers has yet to be achieved. One of the reasons for such hurdle is a lack of suitable CAR targets in solid cancers.

Methods

GM2 is one of the gangliosides, a group of glycosphingolipids with sialic acid in the glycan, and overexpressed in various types of solid cancers. In this study, by using interleukin (IL)‐7 and chemokine (C‐C motif) ligand 19 (CCL19)‐producing human CAR‐T system which we previously developed, a possibility of GM2 as a solid tumor target for CAR‐T cell therapy was explored in a mouse model with human small‐cell lung cancer.

Results

Treatment with anti‐GM2 IL‐7/CCL19‐producing CAR‐T cells induced complete tumor regression along with an abundant T cell infiltration into the solid tumor tissue and long‐term memory responses, without any detectable adverse events. In addition, as measures to control cytokine‐release syndrome and neurotoxicity which could occur in association with clinical use of CAR‐T cells, we incorporated Herpes simplex virus‐thymidine kinase (HSV‐TK), a suicide system to trigger apoptosis by administration of ganciclovir (GCV). HSV‐TK‐expressing anti‐GM2 IL‐7/CCL19‐producing human CAR‐T cells were efficiently eliminated by GCV administration in vivo.

Conclusions

Our study revealed the promising therapeutic efficacy of anti‐GM2 IL‐7/CCL19‐producing human CAR‐T cells with an enhanced safety for clinical application in the treatment of patients with GM2‐positive solid cancers.
Accelerated epigenetic aging and myopenia in young adult cancer survivors
Authors: Gehle Stephanie C. , Kleissler Daniel , Heiling Hillary , Deal Allison , Xu Zongli , Ayer Miller Vanessa L. , Taylor Jack A. , Smitherman Andrew B.
Published: April 2023

Background

Young adult cancer survivors experience early aging‐related morbidities and mortality. Biological aging biomarkers may identify at‐risk survivors and increase our understanding of mechanisms underlying this accelerated aging.

Methods

Using an observational study design, we cross‐sectionally measured DNA methylation‐based epigenetic age in young adult cancer survivors at a tertiary, academic state cancer hospital. Participants were a convenience sample of consecutively enrolled survivors of childhood, adolescent, and young adult cancers treated with either an anthracycline or alkylating agent, and who were at least 3 months post‐treatment. Similarly aged healthy comparators were consecutively enrolled. Cancer treatment and treatment intensity were compared to DNA methylation‐based epigenetic age and pace of aging.

Results

Sixty survivors (58 completing assessments, mean age 20.5 years, range 18–29) and 27 comparators (mean age 20 years, range 17–29) underwent DNA methylation measurement. Survivors were predominantly female (62%) and white (60%) and averaged nearly 6 years post‐treatment (range 0.2–25 years). Both epigenetic age (AgeAccelGrim: 1.5 vs. −2.4, p < 0.0001; AgeAccelPheno 2.3 vs. −3.8, p = 0.0013) and pace of aging (DunedinPACE 0.99 vs. 0.83, p < 0.0001) were greater in survivors versus comparators. In case–case adjusted analysis, compared to survivors with normal muscle mass, myopenic survivors had higher AgeAccelGrim (2.2 years, 95% CI 0.02–4.33, p = 0.02), AgeAccelPheno (6.2 years, 2.36–10.09, p < 0.001), and DunedinPACE (0.11, 0.05–0.17, p < 0.001).

Conclusions

Epigenetic age is older and pace of aging is faster in young adult cancer survivors compared to noncancer peers, which is evident in the early post‐therapy period. Survivors with physiological impairment demonstrate greater epigenetic age advancement. Measures of epigenetic age may identify young adult survivors at higher risk for poor functional and health outcomes.
Anti‐CLL1‐based CAR T‐cells with 4‐1‐BB or CD28/CD27 stimulatory domains in treating childhood refractory/relapsed acute myeloid leukemia
Authors: Pei Kunlin , Xu Haoyu , Wang Pengfei , Gan Wening , Hu Zhengbin , Su Xiaoling , Zhang Hui , He Yingyi
Published: April 2023

Background

Though the efficacy of anti C‐type lectin‐like molecule‐1 (CLL1) CAR T‐cells in refractory/relapsed acute myeloid leukemia (R/R‐AML) have been occasionally reported, the influence of co‐stimulatory domain CAR T‐cells is not investigated so far.

Method

Seven R/R‐AML children treated with anti‐CLL1 CAR T‐cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27‐based CAR T‐cells therapy, and three received 4‐1BB‐based CAR T‐cells therapy.

Result

The overall response rates were 75% and 66.7% in CD28/CD27 and 4‐1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell‐associated neurotoxicity syndrome. The maximum CAR T‐cells durations were 156 and 274 days for CD28/CD27 group and 4‐1BB group respectively. The 1‐yr overall survival rate was 57.1%.

Conclusions

A preliminary similar efficacy/safety index was observed in anti‐CLL1‐based CAR T‐cells with 4‐1BB or CD28/CD27 co‐stimulatory elements in treating pediatric R/R‐AML.
Expression and interpretation of emotions in multilingual psychotherapy: A literature review
Authors: Verkerk Leila , Fuller Janet M. , Huiskes Mike , Schüppert Anja
Published: April 2023

This review aimed at presenting the findings of 19 original studies that were published in the period from 2000 to 2022 in order to outline the current state of the art in the field of emotion communication (i.e., expressing and interpreting emotions) in multilingual psychotherapy. This analysis involves in particular the studies that investigate multilingual phenomena (e.g., code‐switching and language‐mixing) that occur during psychotherapeutic sessions when client and therapist can speak more than one language, as well as the articles that research emotion communication in this multilingual setting. With this in mind, the articles selected for this review are divided into two main categories: linguistic phenomena in multilingual psychotherapy and emotion communication in multilingual psychotherapy. Results of the studies in the current analysis reveal that code‐switching remains one of the main linguistic phenomena that arises in the area of multilingual psychotherapy. Switching languages in therapy tends to be considered as beneficial for both client and therapist. Besides, findings suggest a connection between speaking L1/LX and one's identity (e.g., feeling different depending on the language). Additionally, studies that investigate emotion communication in multilingual psychotherapy show that an individual's first language (L1) is predominantly viewed as more emotionally charged than their language(s) learned later in life (LX). However, some studies also demonstrate that the relationship between L1 and LX is more fluid and context‐dependent than it has traditionally been regarded. Propositions are given for future research in the field of emotion communication in multilingual psychotherapy.
Synthesis, Anti‐Fungal Potency and In silico Studies of Novel Steroidal 1,4‐Dihydropyridines
Authors: Khan Asna , Iqbal Arfeen , Ahmedi Saiema , Manzoor Nikhat , Siddiqui Tabassum
Published: April 2023

Working principle of azoles as antifungals is the inhibition of fungal CYP51/lanosterol‐14α‐demethylase via selective coordination with heme iron. This interaction can also cause side effects by binding to host lanosterol‐14α‐demethylase. Hence, it is necessary to design, synthesize and test new antifungal agents that have different structures than those of azoles and other antifungal drugs of choice in clinical practice. Consequently, a series of steroidal 1,4‐dihydropyridine analogs 16–21 were synthesized and screened for their in vitro anti‐fungal activity against three Candida species as steroids‐based medications have low toxicity, less vulnerability to multi‐drug resistance, and high bioavailability by being capable of penetrating the cell wall and binding to specific receptors. Initially, Claisen–Schmidt condensation takes place between steroidal ketone (dehydroepiandrosterone) and an aromatic aldehyde forming steroidal benzylidene 8–13 followed by Hantzsch 1,4‐dihydropyridine synthesis resulting in steroidal 1,4‐dihydropyridine derivatives 16–21. The results exhibited that compound 17 has significant anti‐fungal potential with an MIC value of 750 μg/ml for C. albicans and C. glabrata and 800 μg/ml for C. tropicalis. In silico molecular docking and ADMET studies were also performed for compounds 16–21.
Advances in Halloysite Nanotubes (HNTs)‐Based Mixed‐Matrix Membranes for CO2 Capture
Authors: Rafiq Sikander , Saeed Muhammad , Jamil Asif , Rashid Muhammad Imran , Irfan Muhammad , Iqbal Tanveer , Inayat Abrar , Jamil Farrukh , Iqbal Jibran , Khurram Muhammad Shahzad , Mehadi Muhammad Shozab
Published: April 2023

Membrane technology promises a highly economical and efficient solution for CO2 separation. Many polymeric membranes have been reported in the past for the separation of gases specially to remove CO2 from natural gas and low‐pressure flue‐gas streams. The performance of membranes can be tailored by dispersing nanofillers in a polymeric matrix to produce mixed‐matrix membranes (MMMs). This not only adds mechanical strength to membranes but also reduces compaction of the polymeric layer at high pressure and maintains high performance. Halloysite nanotubes (HNTs) gained attention in gas separation technology and due to their tubular structure have been used in a variety of applications in biomedical, coating, composite, and electronic industries. However, very little but conclusive literature and reviews are available to indicate that functionalized and non‐functionalized HNTs can improve the performance of MMMs for efficient CO2 capture. The current status and gaps for potential applications of HNTs‐based membranes for gas separation are identified and reviewed.
Cationic Solution and Solid‐State Emitters – Robust Imaging Agents for Cells, Bacteria, and Protists
Authors: Dubbert Justin , Höing Alexander , Graupner Nadine , Rajter Ľubomír , Dunthorn Micah , Knauer Shirley K. , Galstyan Anzhela , Rizzo Fabio , Voskuhl Jens
Published: April 2023

A library of eight different cationic emitters with emission properties in solution and in solid‐state (solution and solid‐state emitters – SSSE) is presented. These compounds, bearing either ammonium or pyridinium groups, have been investigated regarding their photophysical properties as well as their potential application in biological imaging. Besides high quantum yields as well as a high degree of stability during the imaging process, it was additionally revealed that a broad range of biological targets can be addressed, such as different bacterial strains, human cells as well as protists. The reported SSSE approach employing the mentioned robust emitters for biological imaging, will contribute to a rapid and facile way to design and apply affordable emitters with outstanding properties. Additionally, these emitters will overcome the drawbacks of classical luminophores and agents featuring well‐known aggregation‐induced emission (AIE) or aggregation‐caused quenching (ACQ) properties.
Enhanced Performance of CsPbIBr2 Perovskite Solar Cell by Modified Zinc Oxide Nanorods Array with [6,6]‐Phenyl C61 Butyric Acid
Authors: Yang Jien , Zhang Meng , Zhang Qiong , Qin Chaochao , Qin Ruiping , Jain Sagar M. , Liu Hairui
Published: April 2023

Although Metal oxide ZnO is widely used as electron transport layers in all‐inorganic PSCs due to high electron mobility, high transmittance, and simple preparation processing, the surface defects of ZnO suppress the quality of perovskite film and inhibit the solar cells’ performance. In this work, [6,6]‐Phenyl C61 butyric acid (PCBA) modified zinc oxide nanorods (ZnO NRs) is employed as electron transport layer in perovskite solar cells. The resulting perovskite film coated on the zinc oxide nanorods has better crystallinity and uniformity, facilitating charge carrier transportation, reducing recombination losses, and ultimately improving the cells’ performance. The perovskite solar cell with the device configuration of ITO/ZnO nanorods/PCBA/CsPbIBr2/Spiro‐OMeTAD/Au delivers a high short circuit current density of 11.83 mA cm−2 and power conversion efficiency of 12.05 %.
Exploration of N‐Arylation of Backbone Amides as a Novel Tool for Conformational Modification in Peptides
Authors: Dangi Abha , Kiran Marelli Udaya
Published: April 2023

A set of 15 cyclic‐hexaalanine and 10 cyclic‐pentaalanine peptides containing one or two backbone N‐aryl amide bonds were synthesized by following a combination of solution‐phase and solid‐phase peptide synthesis. NMR‐based conformation studies of these N‐aryl cyclic‐hexaalanine peptides revealed five distinct template conformations with an antiparallel β‐sheet structure; for N‐aryl cyclic‐pentaalanine peptides three template structures were revealed. All the template structures have distinct peptide‐turn features. The conformations in these N‐aryl peptides were compared to those in the commonly studied N‐methyl peptide analogues. We observed that the N‐aryl peptides exhibit a considerable conformational homogeneity, and their conformations differ significantly from those in N‐methyl analogues. We anticipate that the N‐arylation of backbone amides has the potential for application as a novel tool for conformation and physicochemical modification in peptides.