bluuebunny/crossref_metadata_2025 huggingface dataset:
Giving the prostate the boost it needs: Spiral diffusion MRI using a high‐performance whole‐body gradient system for high b‐values at short echo times
Authors: Molendowska Malwina , Mueller Lars , Fasano Fabrizio , Jones Derek K. , Tax Chantal M. W. , Engel Maria
Published: November 2024

Purpose

To address key issues of low SNR and image distortions in prostate diffusion MRI (dMRI) by means of using strong gradients, single‐shot spiral readouts and an expanded encoding model for image reconstruction.

Methods

Diffusion‐weighted spin echo imaging with EPI and spiral readouts is performed on a whole‐body system equipped with strong gradients (up to 250 mT/m). An expanded encoding model including static off‐resonance, coil sensitivities, and magnetic field dynamics is employed for image reconstruction. The acquisitions are performed on a phantom and in vivo (one healthy volunteer and one patient with prostate cancer). The resulting images are compared to conventional dMRI EPI with navigator‐based image reconstruction and assessed in terms of their congruence, SNR, tissue contrast, and quantitative parameters.

Results

Using the expanded encoding model, high‐quality images of the prostate gland are obtained across all b‐values (up to 3 ms/μm2), clearly outperforming the results obtained with conventional image reconstruction. Compared to EPI, spiral imaging provides an SNR gain up to 45% within the gland and even higher in the lesion. In addition, prostate dMRI with single‐shot spirals at submillimeter in‐plane resolution (0.85 mm) is accomplished.

Conclusion

The combination of strong gradients and an expanded encoding model enables imaging of the prostate with unprecedented image quality. Replacing the commonly used EPI with spirals provides the inherent benefit of shorter echo times and superior readout efficiency and results in higher SNR, which is in particular relevant for considered applications.
Musculoskeletal mimics for lumbosacral radiculopathy. Part 1: Theoretical considerations
Authors: Chiodo Anthony E. , Jorgensen Shawn P.
Published: November 2024

The diagnosis of lumbosacral radiculopathy includes the exclusion of common musculoskeletal conditions that can cause similar symptoms. Neurology and physiatry physicians use history taking and physical examination findings to develop a differential diagnosis. Appropriate diagnostic testing is then utilized to narrow down this differential diagnosis to determine a working hypothesis of the cause of a patient's symptoms, leading to a treatment plan. There are stark limitations of patient symptoms and physical examination findings in making the diagnosis of lumbosacral radiculopathy and added value of a combination of symptoms and signs to distinguish patients with lumbosacral radiculopathy from patients with mimic disorders. Diagnostic tests have variable strengths and limitations in helping to confirm this diagnosis, contrasting the high sensitivity and lower specificity of magnetic resonance imaging (MRI) with the high specificity but lower sensitivity of electromyography (EMG). Further complexity is added to the task of making a diagnosis and setting a treatment plan by the fact that these disorders are common and interact with each other; they are present concomitantly in up to 25% of patients presenting for electrodiagnostic evaluation. A companion paper will review common musculoskeletal mimics of lumbosacral radiculopathy and provide tools to anchor testing for those conditions to the traditional neurological evaluation of lumbosacral radiculopathy.
Stimulus‐induced rotary saturation imaging of visually evoked response: A pilot study
Authors: Capiglioni Milena , Beisteiner Roland , Cardoso Pedro Lima , Turco Federico , Jin Baudouin , Kiefer Claus , Robinson Simon Daniel , Federspiel Andrea , Trattnig Siegfried , Wiest Roland
Published: November 2024

Spin‐lock (SL) pulses have been proposed to directly detect neuronal activity otherwise inaccessible through standard functional magnetic resonance imaging. However, the practical limits of this technique remain unexplored. Key challenges in SL‐based detection include ultra‐weak signal variations, sensitivity to magnetic field inhomogeneities, and potential contamination from blood oxygen level‐dependent effects, all of which hinder the reliable isolation of neuronal signals. This pilot study evaluates the performance of the stimulus‐induced rotary saturation (SIRS) technique to map visual stimulation response in the human cortex. A rotary echo spin‐lock (RESL) preparation followed by a 2D echo planar imaging readout was used to investigate 12 healthy subjects at rest and during continuous exposure to 8 Hz flickering light. The SL amplitude was fixed to the target neuroelectric oscillations at that frequency. The signal variance was used as contrast metric, and two alternative post‐processing pipelines (regression‐filtering‐rectification and normalized subtraction) were statistically evaluated. Higher variance in the SL signal was detected in four of the 12 subjects. Although group‐level analysis indicated activation in the occipital pole, analysis of variance revealed that this difference was not statistically significant, highlighting the need for comparable control measures and more robust preparations. Further optimization in sensitivity and robustness is required to noninvasively detect physiological neuroelectric activity in the human brain.
Global Leadership Initiative on Malnutrition criteria: Clinical benefits for patients with gastric cancer
Authors: Zheng Jingxian , Wang Xiaojie , Yu Jiami , Hu Qiaoting , Zhan Zhouwei , Zhou Sijing , Xu Jingjie , Li Qifei , Song Chunhua , Wang Chang , Zhao Qingchuan , Xu Hongxia , Shi Hanping , Guo Zengqing ,   Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) Group
Published: November 2024

Malnutrition is a prevalent condition among patients with gastric cancer and is associated with poor survival outcomes. This study aimed to evaluate the clinical utility of the Global Leadership Initiative on Malnutrition (GLIM) criteria in predicting survival among patients with gastric cancer. The multicenter retrospective cohort study (INSCOC study) included 1406 patients enrolled between December 2012 and April 2020, with follow‐up data collected until June 2023. Various indices for muscle evaluation, such as calf circumference (CC) and body weight–standardized hand grip strength (HGS/W), were used to diagnose malnutrition. Kaplan‐Meier curves were used to analyze the relationship between nutrition status, as defined by GLIM criteria, and survival outcomes in these patients. The analysis revealed that using CC or HGS/W as positive indicators of malnutrition effectively identified patients with survival‐related malnutrition. The incidence of malnutrition was 54.5%, with patients’ median overall survival times of 1169 days for stage I and 575 days for stage II cancer (P < 0.001). Malnutrition was identified as an independent risk factor for survival. Additionally, a nomogram developed through Cox regression analysis demonstrated precise predictive capability, incorporating factors such as tumor node metastasis staging, Karnofsky Performance Status Scale, direct bilirubin levels, and nutrition intervention. The study concludes that the GLIM criteria are effective in diagnosing malnutrition and predicting survival in patients with gastric cancer. Nutrition interventions significantly enhance survival outcomes, underscoring the importance of standardized nutrition treatments in improving patient prognosis.
One hundred‐year secular trends of overweight and obesity in China: effects of age, period, and cohort
Authors: Xie Jinchen , Nie Peng , Sun Mengzi , Chen Xinguang , Xu Tingling , Shi Zumin , Lu Chuntian , Wang Youfa
Published: November 2024

Objective

Obesity has become a major public health problem worldwide and particularly in China. This study examined the secular trend of overweight and obesity in China over the past 100 years.

Methods

Nationwide data from the China Health and Nutrition Survey and the Chinese General Social Survey were used. A generalized binary mixed‐effects model and a weighted quantile sum model were applied.

Results

From 1909 to 2021, the prevalence of overweight and obesity remained stable from 1909 to 1944, experienced a smooth increase from 1945 to 1959 followed by a decline between 1960 and 1974, continued to rise after 1975, and peaked in 2003. The prevalence of overweight (obesity) among Chinese adults increased by 2.68 (6.21) times, from 20.65% (3.10%) in 1993 to 55.33% (19.26%) in 2021, and cohorts born during the Chinese Cultural Revolution (1960–1974) exhibited the lowest risk of overweight and obesity, associated with low protein intake and high physical activity. Cohorts born during the Reform and Opening‐Up period (1975–2003) showed a high risk of overweight and obesity related to favorable socioeconomic status and rapid urbanization. Persistent differences by sex and emerging differences by socioeconomic status in overweight and obesity prevalence were captured.

Conclusions

Overweight and obesity trends in China have shown a distinctive increasing–decreasing–increasing pattern over the past 100 years. These patterns exhibit unique characteristics and are influenced by discernible social forces.
Machine learning‐based clustering identifies obesity subgroups with differential multi‐omics profiles and metabolic patterns
Authors: Anwar Mohammad Y. , Highland Heather , Buchanan Victoria Lynn , Graff Mariaelisa , Young Kristin , Taylor Kent D. , Tracy Russell P. , Durda Peter , Liu Yongmei , Johnson Craig W. , Aguet Francois , Ardlie Kristin G. , Gerszten Robert E. , Clish Clary B. , Lange Leslie A. , Ding Jingzhong , Goodarzi Mark O. , Chen Yii‐Der Ida , Peloso Gina M. , Guo Xiuqing , Stanislawski Maggie A. , Rotter Jerome I. , Rich Stephen S. , Justice Anne E. , Liu Ching‐ti , North Kari
Published: November 2024

Objective

Individuals living with obesity are differentially susceptible to cardiometabolic diseases. We hypothesized that an integrative multi‐omics approach might improve identification of subgroups of individuals with obesity who have distinct cardiometabolic disease patterns.

Methods

We performed machine learning‐based, integrative unsupervised clustering to identify proteomics‐ and metabolomics‐defined subpopulations of individuals living with obesity (BMI ≥ 30 kg/m2), leveraging data from 243 individuals in the Multi‐Ethnic Study of Atherosclerosis (MESA) cohort. Omics that contributed to the observed clusters were functionally characterized. We performed multivariate regression to assess whether the individuals in each cluster demonstrated differential patterns of cardiometabolic traits.

Results

We identified two distinct clusters (iCluster1 and 2). iCluster2 had significantly higher average BMI values, fasting blood glucose, and inflammation. iCluster1 was associated with higher levels of total cholesterol and high‐density lipoprotein cholesterol. Pathways mediating cell growth, lipogenesis, and energy expenditures were positively associated with iCluster1. Inflammatory response and insulin resistance pathways were positively associated with iCluster2.

Conclusions

Although the two identified clusters may represent progressive obesity‐related pathologic processes measured at different stages, other mechanisms in combination could also underpin the identified clusters given no significant age difference between the comparative groups. For instance, clusters may reflect differences in dietary/behavioral patterns or differential rates of metabolic damage.
Changes in anthropometry, adiposity, and inflammation in Black and White women engaged in intentional weight loss
Authors: Felix Ashley S. , Sinnott Jennifer A. , Caan Bette J. , Gillespie Shannon L. , Meade Caitlin E. , Strafford Katherine E. , Cosgrove Casey M. , Soma Loriana , Noria Sabrena , Bixel Kristin L. , Salani Ritu , Nagel Christa I. , Chambers Laura M. , Cohn David E. , Suarez Adrian A. , Paskett Electra D.
Published: November 2024

Objective

We examined associations among changes in anthropometry, regional adiposity, and inflammatory markers in Black and White women participating in intentional weight loss.

Methods

A total of 104 women with BMI ≥ 25 kg/m2 self‐selected bariatric surgery (n = 66) or a diet and exercise program (n = 38). Anthropometric, dual‐energy x‐ray absorptiometry‐quantified regional adiposity, and inflammatory markers (C‐reactive protein [CRP], tumor necrosis factor α [TNF‐α], soluble TNF receptor I [sTNFRI], sTNFRII, interleukin [IL]‐6, and soluble IL‐1 receptor antagonist) were measured at baseline and 6 months.

Results

Weight, BMI, visceral adipose tissue, and regional (android and gynoid) adiposity declined in the bariatric surgery group. Among bariatric surgery participants, Black women experienced declines of lesser magnitude in terms of weight and BMI than White women, but changes in regional adiposity and visceral adipose tissue did not differ. In the bariatric surgery group, decreases in weight and BMI were associated with decreases in CRP and IL‐6 among White women, but not Black women. Decreases in weight, BMI, and android fat were associated with increases in TNF‐α, sTNFRI, and sTNFRII among Black women, but not White women.

Conclusions

Decreases in anthropometry and adiposity were observed among Black and White bariatric surgery participants; however, associations among changes in adiposity, anthropometry, and inflammation differed by race.
Cardiometabolic characteristics of weight cycling: results from a mid‐South regional comprehensive health care system
Authors: Swartz Alison Z. , Wood Kathryn , Farber‐Eger Eric , Petty Alexander , Silver Heidi J.
Published: November 2024

Objective

The objective of this study was to determine the unique clinical and cardiometabolic risk characteristics of weight‐cyclers and identify differences between weight‐cyclers and individuals with other weight‐change trajectories.

Methods

A deidentified database of 1,428,204 Vanderbilt University Medical Center patients from 1997 to 2020 was included based on having ≥5 years of recorded weights. Patients with a history of malignant neoplasm, bariatric surgery, implausible BMI (e.g., <15 or >80 kg/m2), or missing documented height were excluded, yielding 83,261 participants categorized by weight trajectory, i.e., weight‐stable, weight‐gainer, weight‐loser, or weight‐cycler, based on criteria of ≥5% weight‐change thresholds. Additionally, quartiles of average successive weight variability were evaluated to determine the effect of absolute differences among successive weight values.

Results

Over half (55%) of participants were weight‐cyclers, 23% were weight‐gainers, 12% were weight‐losers, and 10% were weight‐stable over 5 years. Although baseline BMI did not differ among groups, weight‐cyclers were more likely to have lower high‐density lipoprotein cholesterol and higher blood glucose and triglyceride levels and to have been prescribed antihypertensive, dyslipidemia, and/or antidiabetic therapies. They were also younger and more likely to be smokers. Participants with the greatest weight variability (i.e., highest quartile of average successive weight variability) had higher cardiometabolic risk scores.

Conclusions

Weight cycling was highly prevalent but yielded no meaningful overall change in body weight after 5 years. These findings support a paradigm shift in weight management in individuals with overweight/obesity toward reducing cardiometabolic risk with or without weight loss.
Early changes in the gut microbiota are associated with weight outcomes over 2 years following metabolic and bariatric surgery
Authors: Steffen Kristine J. , Sorgen Alicia A. , Fodor Anthony A. , Carroll Ian M. , Crosby Ross D. , Mitchell James E. , Bond Dale S. , Heinberg Leslie J.
Published: November 2024

Objective

Metabolic and bariatric surgery (MBS) is associated with substantial, but variable, weight outcomes. The gut microbiome may be a factor in determining weight trajectory, but examination has been limited by a lack of longitudinal studies with robust microbiome sequencing. This study aimed to describe changes in the microbiome and associations with weight outcomes more than 2 years post surgery.

Methods

Data were collected at two Midwestern U.S. centers. Adults undergoing primary MBS were assessed before and 1, 6, 12, 18, and 24 months after surgery. BMI and metagenomic sequencing occurred at each assessment. A linear growth mixture model determined class structure for weight trajectory.

Results

A linear growth mixture model of participants (N = 124) revealed a two‐class structure; one class had greater sustained weight loss relative to the other. Greater genus‐level taxonomic changes in the microbiome composition at each time point were associated with being in the more favorable weight trajectory class, after controlling for surgery type. Higher Proteobacteria relative abundance at 1 month was predictive of percentage weight change at 6, 12, 18, and 24 months (p < 0.05 for all).

Conclusions

Greater genus‐level taxonomic changes in the gut microbiota are associated with improved weight trajectory. Early changes in the gut microbiota may be an important indicator of MBS outcomes and durability.
Untying the knot: Unraveling genetic mechanisms behind black knot disease resistance in Prunus salicina (Japanese plum)
Authors: Shum Chloe , Najafabadi Mohsen , de Ronne Maxime , Torkamaneh Davoud , El Kayal Walid , Subramanian Jayasankar
Published: November 2024

Little is known regarding the genes, compounds and physiological alternations that take place upon infection of black knot disease. This research aimed to unravel the genetic mechanism responsible for the resistance of Japanese plum (Prunus salicina L.) trees against black knot (Apiosporina morbosa Schwein.) using a Genome‐Wide Association Study. Genotyping by Sequencing (GBS) was combined with a phenotyping system to analyze 200 genotypes of mixed origin. Population stratification identified four subpopulations, and the Fixed and Random Model Circulating Probability Unification (FarmCPU) algorithm was used for this analysis. Nineteen single nucleotide polymorphisms (SNPs) significantly associated with black knot disease resistance were discovered across five chromosomes. Linkage disequilibrium analysis identified 55 genes near these SNPs, with eight genes related to plant defense, immunity, and biotic stress response. One SNP mutation was found in the 5′ untranslated region of a gene regulating the first enzyme in phenylpropanoid biosynthesis. The results provide valuable insights into the genetic mechanisms behind BLACK KNOT disease resistance in Japanese plum and identifies potential markers for use in molecular breeding.
Achieving optimum balance between mechanical properties and gloss of acrylonitrile–styrene–acrylate resin through control of rubber particle size distribution
Authors: Yao Xinyu , Liu Mengen , Tang Qianyi , Zuo Yansheng , Liu Baijun , Zhang Mingyao
Published: November 2024

Preparation of acrylonitrile–styrene–acrylate (ASA) with high gloss and superior impact properties is still challenging. Here, we developed a new strategy for the preparation of ASA resins by a selective redox initiation method based on a semi‐continuous emulsion polymerization technique. A series of ASA core‐shell impact modifiers were firstly obtained by grafting styrene (St) and acrylonitrile (AN) onto poly(n‐butyl acrylate) (PBA) seeded latexes of different sizes. The ASA core‐shell impact modifier was then used to toughen the styrene–acrylonitrile copolymer (SAN). The synergistic effects between the single particle size of the rubber phase and different particle sizes were systematically investigated, and the mechanical properties of SAN‐toughened resins at various particle sizes of the rubber phase were analyzed. The results revealed that toughened SAN with small particle sizes possessed better gloss, and the impact strength of the doped small‐particle toughened SAN was much higher than that of the single particle size toughened SAN. The ASA graft powders synthesized from large particle PBA (particle size 316 nm) and small particle PBA (particle size 99 nm), respectively, were mixed at a 50/50 ratio and blended with SAN resin, a gloss level reaching 95, and an impact performance of 275 J/m values almost twice those of a single particle size toughened SAN.

Highlights

Acrylonitrile–styrene–acrylate resins with an impact strength of 275 J/m and gloss of 95 were prepared.

The balance between mechanical properties and gloss of acrylonitrile–styrene–acrylate resin was obtained.

Polymerization was initiated at low temperature.
Cannabinoids for obstructive sleep apnea: A systematic review
Authors: Boylan Paul M. , Santibañez Melissa , Thomas Jennifer , Weeda Erin , Noel Zachary R. , Caballero Joshua
Published: November 2024

Cannabinoids have emerged as a potential treatment for obstructive sleep apnea (OSA). This systematic review aimed to summarize the efficacy and safety of cannabinoids to treat OSA. Databases including Ovid MEDLINE, EMBASE, Scopus, PsycINFO, and International Pharmaceutical Abstracts were searched; experimental and observational studies were eligible for inclusion. One‐hundred seventy unique records were screened, and nine studies included: five full‐text studies and four published abstracts. The five full‐text studies were judged for quality appraisal: two studies deemed at low risk for bias, one study deemed to have some concerns for bias, and two studies deemed to have high risk for bias. Seven of nine total studies were experimental designs and evaluated dronabinol, and the other two studies were observational designs evaluating cannabis. The range of cannabinoid therapy duration spanned from 1 to 6 weeks, and the median duration was 3 weeks. Eight of nine total studies reported statistically significant, positive OSA outcomes due to cannabinoid therapy including reductions in the apnea hypopnea index and improvements in patient‐reported daytime sleepiness scales. Between 70% and 80% of study participants reported neuropsychiatric and gastrointestinal adverse events attributable to cannabinoids. The American Academy of Sleep Medicine does not recommend using cannabinoids to treat OSA due to a lack of long‐term safety and efficacy data. This systematic review found similar limitations, with the median cannabinoid treatment duration being only 3 weeks. Adequately powered experimental trials over longer time frames are necessary to more completely assess the long‐term efficacy and safety of cannabinoids in the treatment of OSA and its effects on common comorbid conditions, such as obesity and cardiovascular disease.
Solid‐Solid Phase Transformation Behavior of ϵ‐CL‐20 Induced by Typical Organic Solvents: A Theoretical and Experimental Study
Authors: Guo Ya , Xu Duoxue , Guo Zhicheng , Huang Qi
Published: November 2024

The solid‐solid phase transformation of ϵ‐CL‐20 induced by external conditions is one of the bottlenecks limiting the widespread applications of CL‐20‐based energetic materials. Herein, we report the investigation on the influence of solvent polarity on ϵ‐CL‐20 solid‐solid phase transformation behavior both theoretically and experimentally. Density functional theory (DFT) calculation was performed to evaluate the possibility of ϵ‐CL‐20 phase transformation induced by organic solvent molecules from the perspective of ϵ‐CL‐20 electronic structure and molecular structure variations. Additionally, experimental study of ϵ‐CL‐20 phase transformation induced by 1,2‐dichloroethane, ethanol, and methanol gas environment was conducted. Solvent with higher polarity was confirmed to significantly vary molecular surface electrostatic potential and molecular conformation of ϵ‐CL‐20 molecule. Furthermore, ϵ‐CL‐20 critical phase transformation temperature decreased when using inducing solvent with higher polarity. And the observed maximum phase transformation rate was the one induced by the highest polarity solvent. A four‐parameter model was established to describe the phase transformation process as a function of time based on the experimental results. Possible ϵ‐CL‐20 solid‐solid phase transformation mechanism was proposed. Hopefully, these results will be beneficial for the rational preparation and utilization of CL‐20‐based energetic materials.
Exploring the Dynamic Interplay of Deleterious Variants on the RAF1–RAP1A Binding in Cancer: Conformational Analysis, Binding Free Energy, and Essential Dynamics
Authors: Khan Abbas , Ali Syed Shujait , Zahid Muhammad Ammar , Abdelsalam Shahenda Salah , Albekairi Noorah , Al‐Zoubi Raed M. , Shkoor Mohanad , Wei Dong‐Qing , Agouni Abdelali
Published: November 2024

The RAF1–RAP1A interaction activates the MAPK/ERK pathway which is very crucial in the carcinogenesis process. This protein complex influences tumor formation, proliferation, and metastasis. Understanding aberrant interactions driven by clinical mutations is vital for targeted therapies. Hence, the current study focuses on the screening of clinically reported substitutions in the RAF1 and RAP1A genes using predictive algorithms integrated with all‐atoms simulation, essential dynamics, and binding free energy methods. Survival analysis results revealed a strong association between RAF1 and RAP1A expression levels and diminished survival rates in cancer patients across different cancer types. Integrated machine learning algorithms showed that among the 134 mutations reported for these 2 proteins, only 13 and 35 were classified as deleterious mutations in RAF1 and RAP1P, respectively. Moreover, one mutation in RAF1 reported elevated levels of binding between RAF1 and RAP1P while in RAP1A, 7 mutations were reported to increase the binding affinity. The high‐binding mutations, P34Q and V60F, were subjected to protein–protein coupling which confirmed the increase in the binding affinity. Wild‐type and mutant RAF1–RAP1P bound complexes were subjected to molecular simulation investigation, revealing enhanced structural stability, increased compactness, and stabilized residue fluctuations of the mutant systems in contrast to the wild‐type. In addition, hydrogen bonding analysis revealed a variation in the binding paradigm which further underscores the impact of these substitutions on the coupling of RAF1 and RAP1A. Principal component analysis (PCA) and free energy landscape (FEL) evaluation further determined dynamical variations in the wild‐type and mutant complexes. Finally, the Gibbs free energy for each complex was estimated and found to be −71.94 ± 0.38 kcal/mol for the wild‐type, −95.57 ± 0.37 kcal/mol for the V60F, and −85.76 ± 0.72 kcal/mol for P34Q complex. These findings confirm the effect of these variants on increasing the binding affinity of RAF1 to RAP1P. These mutations can therefore be targeted for cancer therapy to modulate the activity of the MAPK/ERK signaling pathway.
Superior target genes and pathways for RNAi‐mediated pest control revealed by genome‐wide analysis in the beetle Tribolium castaneum
Authors: Buer Benjamin , Dönitz Jürgen , Milner Martin , Mehlhorn Sonja , Hinners Claudia , Siemanowski‐Hrach Janna , Ulrich Julia K. , Großmann Daniela , Cedden Doga , Nauen Ralf , Geibel Sven , Bucher Gregor
Published: November 2024

BACKGROUND

An increasing human population, the emergence of resistances against pesticides and their potential impact on the environment call for the development of new eco‐friendly pest control strategies. RNA interference (RNAi)‐based pesticides have emerged as a new option with the first products entering the market. Essentially, double‐stranded RNAs targeting essential genes of pests are either expressed in the plants or sprayed on their surface. Upon feeding, pests mount an RNAi response and die. However, it has remained unclear whether RNAi‐based insecticides should target the same pathways as classic pesticides or whether the different mode‐of‐action would favor other processes. Moreover, there is no consensus on the best genes to be targeted.

RESULTS

We performed a genome‐wide screen in the red flour beetle to identify 905 RNAi target genes. Based on a validation screen and clustering, we identified the 192 most effective target genes in that species. The transfer to oral application in other beetle pests revealed a list of 34 superior target genes, which are an excellent starting point for application in other pests. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses of our genome‐wide dataset revealed that genes with high efficacy belonged mainly to basic cellular processes such as gene expression and protein homeostasis – processes not targeted by classic insecticides.

CONCLUSION

Our work revealed the best target genes and target processes for RNAi‐based pest control and we propose a procedure to transfer our short list of superior target genes to other pests. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
The horizontal and vertical controls on the thermal structure of the tropical troposphere
Authors: Palmer L. A. , Singh M. S.
Published: November 2024

Our conceptual understanding of the tropical thermal structure is based on two complementary idealisations: one stemming from convective quasi‐equilibrium (QE) and the other being the weak temperature gradient (WTG) approximation. Through QE, moist convection provides a vertical control on the thermal structure, while, under WTG, wave dynamics are assumed to provide a non‐local horizontal control. While it is clear that moist convection plays an important role in setting the tropical mean stability through QE, the extent to which QE implies a local constraint on stability or whether the requirement for WTG effectively inhibits the influence of local conditions on stability remains debated. Here we hypothesise that a strong local vertical control of the thermal structure would imply a relationship between humidity and stability in the troposphere, as convection within moister regions would be less affected by entrainment of surrounding air. We utilise a combination of ERA5 reanalysis and observational data to examine the relationship between stability and local humidity across the Tropics. The results are compared with a prediction based upon a specific realisation of the theory of QE that incorporates entrainment through a simple plume model. We discover that, in convective regions, wave dynamics do not eliminate the effect of local conditions on stability, and that the resulting relationship between stability and humidity can be approximated well by the entraining plume model. Since QE is not applicable in the absence of convection, in non‐convective regions the WTG, and possibly other factors, acts to set stability in the region. These results may help us understand the controls on horizontal density gradients in the tropical troposphere and the associated overturning circulations.
Two Erigeron species comparison based on their ingredient profile by UPLC‐PDA‐QTOF‐MS/MS and discriminant analysis
Authors: Zhang Jianguang , Wang Yue , Wulu Jiansang , Jin Wenfang , Yang Qing , Zhang Zhifeng
Published: November 2024

Rationale

Erigeron breviscapus (EB) and Erigeron multiradiatus (EM) are the two species of the genus Erigeron (Asteraceae) with extremely close genetic relationships. They were used as the same “meiduoluomi” for the treatment of plague and epidemics in traditional Tibetan medicine. But in traditional Chinese medicine, only EB is used for treatment of cerebrovascular obstruction, hemiplegia due to stroke, coronary artery obstruction, chest congestion, and angina pectoris. These two Erigeron species show different effects in different traditional medicine systems. Therefore, analyzing the chemical compositions of two species will not only enhance comprehension of their medicinal properties but also foster the advancement and exploration of novel applications. However, to date, there has been no comprehensive and detailed investigation comparing the constituents of EB and EM.

Methods

A methodology for rapid identification of chemical profiles from two Erigeron species was devised through the integration of ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry (UHPLC‐QTOF‐MS/MS) and multivariate statistical analysis. Additionally, a UHPLC‐photo‐diode array (PDA) method was established to precisely quantify of 11 components.

Results

A total of 58 constituents comprising flavonoids, phenolic acids, saponin, and long chain fatty acids were elucidated. Thirteen compounds were identified as potential differentiators in chemical profiles among the two Erigeron species. For quantitative assessment, 11 bioactive compounds were simultaneously quantified across 49 batches of Erigeron species samples utilizing UHPLC‐PDA with wavelengths of 325, 254, and 266 nm. The method demonstrated excellent precision, linearity, accuracy, repeatability, stability, and recovery.

Conclusions

The findings from this study will serve as a reference for quality control, functional activity exploration, and improved clinical application based on the ingredient profiles of the two species. Furthermore, this inaugural investigation into the ingredient profiles of these two species will enhance the potential and optimal utilization of both EB and EM resources.
Green Fruit‐Stem Pairing and Clustering for Machine Vision System in Robotic Thinning of Apples
Authors: Hussain Magni , He Long , Schupp James , Lyons David , Heinemann Paul
Published: November 2024

Apples are one of the most highly‐valued specialty crops in the United States. Recent labor shortages have made crop production difficult for fruit growers, including the task of green fruit thinning. Current methods including hand, chemical, and mechanical thinning impose tradeoffs between selectivity, cost, tree damage, and speed. A robotic green fruit thinning system could potentially selectively thin fruit in a quick, cost‐effective, and non‐damaging manner. The machine vision system would be a critical component for robotic thinning, and would not only need to perform green fruit detection/segmentation, but also fruit‐stem pairing and clustering to facilitate proper decision‐making for thinning. A neural network‐based fruit and stem pairing algorithm was devised and evaluated; an LSTM‐based clustering algorithm was devised and compared to the density‐based clustering algorithm, OPTICS. The algorithms were evaluated on an image data set consisting of GoldRush, Fuji, and Golden Delicious cultivars at the green fruit stage, with evaluations on overall performance, cultivar‐wise performance, cluster size‐specific performance, and feature importance. For fruit and stem pairing, the neural network‐based pairing algorithm achieved an AP of 81.4% on all fruits and stems, and that reached 90.6% when only fruits and stems with labeled angles were considered. For green fruit clustering, the LSTM‐based clustering achieved a clustering success rate of 68.4%, whereas the OPTICS algorithm obtained 50.9%. The algorithms will be further implemented in a pipeline of a future green fruit thinning vision system, as well as integrate the use of point clouds and other 3D orchard information to improve pairing and clustering performance.
Consumer preferences toward new circular bioeconomy agri‐food products
Authors: Villanueva Anastasio J. , Salazar‐Ordóñez Melania , Granado‐Díaz Rubén
Published: November 2024

The integration of circular bioeconomy (CB) principles into food production is key for a sustainable food sector. This research analyzes consumers' preferences for food products that include CB‐related attributes; namely, zero (plastic/bio) waste generation, carbon neutrality, sustainable water use and soil management, biodiversity conservation, and contribution to the rural economy. A novel approach is applied, combining best‐worst scaling choice experiments with contingent valuation and using a scale‐adjusted latent class model specification. The results reveal consumers have intense preferences for CB attributes in food, especially those related to plastic waste management, sustainable water use, rural development, and biodiversity. Four different consumer classes are identified according to their preferences toward CB attributes (Eco‐multifunctionals, Utilitarians, Sustainable agrarians, and Circulars—the latter two newly identified here). Willingness to pay varies by attribute and class. Relevant implications are drawn for businesses, especially about potential differentiation marketing strategies.
Anticancer Potential of Piperidine Containing Small Molecule Targeted Therapeutics
Authors: Saini Nidhi , Goswami Vishalgiri , Thakor Ekta , Vasava Mahesh , Patel Bhumika
Published: November 2024

In the past two decades, targeted anti‐cancer therapeutics have achieved remarkable success due to their exceptional advantages of selectivity towards cancer cells and safety. Targeted small molecule anti‐cancer therapies persisted in many barriers; majorly poor response to drug therapy. Piperidine, a heterocyclic moiety, exceeds twenty instances of other pharmaceutical classes and natural compounds in the form of alkaloids effective in anti‐cancer treatment. The current review focuses on recent advancements, mainly from 2017–2023, of piperidine‐containing small molecule development as anti‐cancer agents. Total 10 piperidine containing anti‐cancer drugs have been approved by USFDA since 2017 to till date and around 15 small molecule anti‐cancer inhibitors containing piperidine scaffold which are in their early discovery phase have been reviewed which are classified according to their biological target. It highlights the structural contribution of piperidine ring towards the enhancement of activity or pharmacokinetic properties of diverse biological target‐specific anti‐cancer inhibitors of angiogenesis, EGFR, VEGFR, ALK, AKT1, topoisomerase, CDK2 etc. The role of the piperidine ring in enhancing potency, selectivity and bioavailability of novel molecules has been discussed. This review will be helpful to researchers, especially medicinal chemists, for the designing of piperidine‐containing potent drugs for specific biological targets for cancer.
Synthesis, Biological Evaluation, and Molecular Docking Study of Novel 5‐Substituted 1,2,4‐Oxadiazole‐3‐yl Benzoxazole Derivatives as Potential Antimicrobial Agents
Authors: Gadakh Sandip , Prajapati Dhaval , Aghav Balasaheb
Published: November 2024

Discovery of novel antimicrobial drugs is one of the hottest topics in the field of medicinal chemistry. An efficient and catalyst free synthesis of novel fluorinated 5‐substituted 1,2,4‐oxadiazole‐3‐yl benzoxazole derivatives is described. A series of novel compounds have been synthesized and characterized by different spectroscopic techniques such as FTIR, 1H NMR, 13C NMR, and LCMS. When tested for antibacterial activity, the synthesized benzoxazole derivatives exhibited outstanding to good activities in comparison to the conventional medications. Moreover, the theoretical forecasts grounded in molecular docking against microbial DNA gyrase may offer a glimpse into the conceivable mode of operation and establish a connection between the detected antimicrobial efficacy and the binding affinity, illuminating particular thermodynamic (bonded and nonbonded) interactions that regulate the activity. The produced compounds also exhibited promising qualities to develop into viable oral medication candidates when their absorption, distribution, metabolism, and excretion were examined. In summary, the research proposes that these novel compounds have emerged as interesting contender for the development of next generation antimicrobial drugs. Our protocol demonstrates broad substrate scope, dramatic decrease of synthesis time, and energy consumption with excellent yields.
NH4Ca[B5O7(OH)4] H2O: A Biaxial Mixed‐Cation Pentaborate with Moderate Birefringence
Authors: Lin Ming‐Sui , Li Wen‐Hui , Wu Hong‐Yan , Liu Xia , Lai Wen‐Zhong , Zhang Jian‐Han
Published: November 2024

Ammonium‐calcium mixed‐cation pentaborate NH4Ca[B5O7(OH)4]·H2O has been synthesized for the first time. Single‐crystal X‐ray diffraction analysis reveals that it crystallizes in the triclinic space group P‐1 with lattice parameters a = 6.7042(3) Å, b = 7.1859(3) Å, c = 10.7447(4) Å, α = 100.304(3), β = 97.774(3), γ = 96.972(3). The structure is characterized by 1D boron–oxygen chains composed of [B5O7(OH)4]3− polyanions that are further interspaced by Ca2+, NH4+ cations, along with lattice water molecules. The phase purity and thermal stability of the as‐synthesized sample were confirmed by XPRD and TG‐DSC analyses. Experimental UV–vis diffuse reflectance spectroscopy coupled with Urbach fitting indicates a direct bandgap of 4.50 eV, contrasting with theoretical calculations that suggest an indirect bandgap of 5.53 eV. Additionally, both theoretical computation and polarized light experimental test indicate that NH4Ca[B5O7(OH)4]·H2O exhibits moderate birefringence.
Polyphenol Tannin‐Induced Protein Precipitation for Drug Target Discovery by Chemical Proteomics
Authors: Gao Yujun , Zhang Xiaolei , Ye Mingliang , Hu Lianghai
Published: November 2024

High‐throughput drug discovery is highly dependent on the targets available to accelerate the process of candidate screening. Unbiased drug target identification is of crucial importance to reveal the mechanisms of protein–drug interactions. In recent years, energetics‐based protein conformation methods have become an alternative strategy for protein target discovery of bioactive drugs. In this study, we present a novel tannin protein precipitation method (TAP) for identifying target proteins of small molecules using the effect on protein solubility of tannin. The feasibility of this method was validated using a drug model of methotrexate. It was found that the known target DHFR yields a significant solubility shift. This method was further investigated with Annexin A2, the target protein of protopanaxadiol (PPD)‐S by western blot, and by screening potential target proteins of PPD‐S in K562 cells by quantitative proteomics. Finally, the TAP method was employed to differentiate the target proteins of pair chiral molecules PPD‐S and PPD‐R, which can bring up novel insights into the mechanism of drug–protein interactions. This study not only provides an effective tool for drug research and development but also offers new ideas for understanding the mechanism of action of natural chiral bioactive compounds.
Capturing Hydrophilic Chemotherapeutics Agents Into siRNA‐Encapsulated Vesicle‐Like Nanoparticles for Convenient ICB‐Chemo Combination Therapy
Authors: Li Yan , Li Bingqin , Chen Chaoran , Hou Hengliang , Su Miao , Li Fangzheng , Xiao Zekai , Yang Xianzhu
Published: November 2024

Clinical evidence has demonstrated that combining immune checkpoint blockade (ICB) therapy with chemotherapy significantly improves response rates to ICB therapy and therapeutic efficacy in various tumor types. However, a convenient method for achieving synergistic ICB therapy and chemotherapy with precise co‐delivery of both agents is still highly desirable. In this study, a strategy for co‐delivering small interfering RNA (siRNA) encapsulated in vesicle‐like nanoparticles (VNPsiRNA) and chemotherapeutic drugs is aimed to develop. It is discovered that the hydrophilic chemotherapeutic drug mitoxantrone hydrochloride (MTO·2HCl) can be captured into VNPsiRNA. The resulting VNPsiRNACpMTO can simultaneously block immune checkpoints via RNA silencing and induce chemotherapeutic effects on tumor cells. The mechanism of MTO·2HCl is elucidates, captures, and demonstrates the superior therapeutic effect of VNPsiRNACpMTO through chemo‐immunotherapy. This strategy can also be extended to deliver other hydrochloride anticancer drugs, such as doxorubicin hydrochloride (DOX·HCl), for achieving synergistic combination therapy. This study provides a facile strategy for enhancing combined ICB and chemotherapy via co‐delivering siRNA and chemotherapeutic drugs, offering a promising approach to cancer treatment.
2D‐Penta‐PdPS: Gate‐Tunable and Thickness‐Dependent Thermoelectric Transport
Authors: Yip Weng Hou , Fu Qundong , Wang Xingli , Duan Ruihuan , Liu Zheng , Boutchich Mohamed , Tay Beng Kang
Published: November 2024

Pentagonal two‐dimensional (2D) materials are notable for unique properties derived from their Cairo pentagonal tiling topology. This study explores the thermoelectric potential of exfoliated penta‐palladium‐phosphorus‐sulfur (PdPS) atomic layers, an air‐stable 2D semiconductor with a puckered pentagonal low‐symmetry structure, grown via chemical vapor transport (CVT). Thickness‐dependent in‐plane electrical conductivity (σ) and thermoelectric power factor (PF) of PdPS are investigated from 20–380 K, showing an increase in σ with thickness (11, 13, and 88‐layer). Applying back‐gate voltage (Vg) modulates the Fermi energy (EF), and as Vg decreases, the Seebeck coefficient (S) rises, achieving S of −700 µV K−1 for 11‐layer PdPS at −10 V, significantly higher than the −400 µV K−1 for 88‐layer PdPS. The PF increased with decreasing thickness, peaking at ≈50 µW m−1 K−2 for 11‐layer PdPS, about twice than that of 88‐layer PdPS. The high electron mobility (µe) in PdPS is confined to a narrow temperature range, peaking at 300 cm2 Vs−1 at 100 K, marking the transition temperature from ionized impurity scattering to acoustic phonon scattering mechanism, consistent across all layer counts. This work highlights the significant impact of quantum confinement in ultrathin bodies in enhancing thermoelectric performance across a wide temperature range.
PEGylated Multimeric RNA Nanoparticles for siRNA Delivery in Traumatic Brain Injury
Authors: Han Sangwoo , Yoo Woojung , Carton Olivia , Joo Jinmyoung , Kwon Ester J.
Published: November 2024

Traumatic brain injury (TBI) impacts millions of people globally, however currently there are no approved therapeutics that address long‐term brain health. In order to create a technology that is relevant for siRNA delivery in TBI after systemic administration, sub‐100 nm nanoparticles with rolling circle transcription (RCT) are synthesized and isolated in order improve payload delivery into the injured brain. Unlike conventional RCT‐based RNA particles, in this method, sub‐100 nm RNA nanoparticles (RNPs) are isolated. To enhance RNP pharmacokinetics, RNPs are synthesized with modified bases in order to graft polyethylene glycol (PEG) to the RNPs. PEGylated RNPs (PEG‐RNPs) do not significantly impact their knockdown activity in vitro and lead to longer blood half‐life after systemic administration and greater accumulation into the injured brain in a mouse model of TBI. In order to demonstrate RNA interference (RNAi) activity of RNPs, knockdown of the inflammatory cytokine TNF‐α in injured brain tissue after systemic administration of RNPs in a mouse model of TBI is demonstrated. In summary, small sub‐100 nm multimeric RNA nanoparticles are synthesized and isolated that can be modified using accessible chemistry in order to create a technology suitable for systemic RNAi therapy for TBI.