Search

Plankton are the foundation of the food chain in aquatic environments, and changes in phytoplankton community structure and function could pose risks to human health through their impacts on pollutant activity. We studied the correlation of plankton community and functional groups to the environmental factors in the Fuhe River, China. Water quality was evaluated based on Qr-index of phytoplankton diversity and functional group biomass. From September 2020 to August 2021, a total of 304 phytoplankton and 158 zooplankton species were collected. The phytoplankton were divided into 30 functional groups, whereas zooplankton were divided into nine functional groups. Phytoplankton functional groups were mainly composed of groups H1, MP, and W1. Among them, functional group MP had the greatest biomass, accounting for 34.37% of the phytoplankton biomass, followed by H1 (10.61%), and W1 (10.10%). The zooplankton functional groups mainly consisted of RF, RC, and SCF functional groups. The functional group RC accounted for 48.81% of the total zooplankton biomass, followed by RF (20.46%), and SCF (19.65%). The major environmental factors influencing phytoplankton functional groups were water temperature (WT), dissolved oxygen (DO), oxidationreduction potential (ORP), and transparency (TS), whereas the major environmental factors influencing zooplankton functional groups were WT, pH, and DO. Overall, water quality of Fuhe River Basin was good, being slightly polluted or pollution-free. [ABSTRACT FROM AUTHOR]

This study determined the effects of salt stress (NaCl) and alkali stress (Na2CO3) on the growth and physiology of Amorpha fruticosa seedlings. The results showed that salt and alkali stress inhibited the growth of root, stem and leaf, but the appropriate concentration of salt and alkali stress could stimulate root elongation. Salt stress and alkali stress resulted in the decrease of photosynthetic capacity of seedlings. The degree of Na+ absorption by the roots is relatively low, and a large amount of Na+ absorbed into the body is separated in the stem and total petiole. The concentration K+, Ca2+ and Mg2+ in diverse plant organs significantly changed under both stresses while concentration of K+, Ca2+ and Mg2+ in leaflets did not change significantly. In addition, accumulation of Cl- under salt stress was not obvious. Soluble sugar accumulation in roots and lobules remarkably increased under both stresses. The distribution of soluble sugar in each vegetative organ was changed. The absorption of degree of harmful ions was relatively low, and more harmful ions were accumulated in the stem and total petiole. This was the response strategy of the seedlings to adapt to salt and alkali stress and it provides a theoretical basis for planting Amorpha fruticosa in areas with relatively low salinization degree. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of application of mind mapping combined with the teaching method of problem-based learning (PBL) in undergraduate teaching of clinical dermatology and venereology. Methods This study included a total of 96 undergraduate students who majored in clinical medicine at Qingdao University, and were interns in the dermatology department of the Affiliated Hospital of Qingdao University. The participants were randomly divided into the experimental group (48 cases, using mind mapping combined with the teaching method of PBL) and the control group (48 cases, using traditional PBL teaching method). After the course, the comprehensive evaluation of teaching effect was carried out through written examination and questionnaire survey. Results The written test scores of experimental group were higher than those of the control group (t=3.10, P

Nano-ZnO/transition metal composites (NZTC) were prepared via sol-gel method where transition metal (Cu2+, Ag+, Co2+ and Ni2+) and ZnSO4 were used as the substrate. NZTC was characterized using scanning electronic microscope (SEM), ultraviolet-visible spectrophotometer (UV), fluorescence spectrophotometer (XRF), infrared spectrometer (IR), and so on. The photocatalytic degradation behaviors of nano-ZnO and NZTC for formaldehyde in gas and solution were investigated. The results indicated that nano-ZnO and NZTC could achieve the degradation of formaldehyde by photocatalytic process, and the degradation rates were up to 43.75% and 67.2% in gas and solution, respectively, thus thereby leading to good application prospects in the degradation of organic compounds.

Abstract The calculation of the spectral blueing operator in the traditional spectral blueing method has singularity, which leads to poor performance in post-stack seimic frequency expansion. To this end, a frequency spreading technique based on matching pursuit (MP) and spectral blueing is proposed. Through time–frequency analysis processing, it is shown that the seismic signal extracted by matching tracking method has good stability and higher resolution. The specific process of the method in this paper firstly uses the matching tracking method to accurately divide the post-stack seismic data into multiple frequency-division seismic bodies; then, in the process of calculating the spectral blueing ization operators for each frequency band, the weighting idea is used to calculate the weights of the optimized spectral blueing ization operators for each frequency band based on the differences in energy in different frequency bands; finally, the optimized spectral blueing operator is convolved with seismic reflection coefficients to obtain high-resolution seismic data. The actual test results of poststack seismic data have proven that the frequency raising method proposed in this paper is superior to the traditional spectral blueing ization algorithm, greatly improving the high-frequency component information of poststack seismic data. After frequency extension, there are more seismic events and higher resolution. Finally, the practicability and rationality of the seismic data after frequency extraction are verified by a series of operations such as attribute extraction, well seismic calibration and inversion.

It is estimated that approximately seven million people worldwide are affected by inflammatory bowel disease (IBD), causing a huge burden on healthcare systems and society. In the occurrence, progression, and treatment of IBD, the intestinal microbiota and its key metabolic product, bile acids, play a crucial role. The intestinal microbiota not only participates in the biotransformation of bile acids, enriching the diversity of bile acids, but also regulates their synthesis and transport through the farnesoid X receptor (FXR). Meanwhile, bile acids contribute to regulating the structure and function of the intestinal microbiota by supporting microbial diversity, exerting direct toxicity, participating in indirect antimicrobial pathways, and influencing microbial metabolic capabilities. Furthermore, under normal physiological conditions, intestinal microbiota-derived bile acids facilitate the repair process of the intestinal epithelial barrier. They also promote the balance of the immune system by modulating the functions of various immune cells including helper T (Th) cells 17, regulatory T (Treg) cells, CD8+ T cells and natural killer T(NKT) cells, thereby slowing down the development of IBD. This article focuses on exploring the role of intestinal microbiota and bile acids in the onset and progression of IBD, and investigating new effective treatment strategies by targeting intestinal microbiota and bile acids, such as bile acid receptor modulators, probiotics, prebiotics, fecal microbiota transplantation (FMT), and phage therapy.

Flowers of Rhododendron have unique poricidal dehiscence anther, but the formation of the dehiscence pore and the mechanism of pollen releasing are not fully known. The purpose of this research was to study the anther development of Rhododendon × pulchrum through microdissection and paraffin section to find out how the dehiscence pore develops and what tissues are involved in its development. The results were as follows: (1) The tissue forming the apical pore and the main body of the anther diverged from the very beginning of the stamen development. The dehiscence pore is formed by breaking down of parenchyma tissue, which is derived from the apical meristem of stamen primordium. The body part of the anther comes from the archesporial cells and they develop into regular pollen sacs with multi-layered anther walls. (2) The anther wall is fully differentiated at the stages from microspore mother cell to microspore tetrad, with 6-7 layers of cells, including 1 layer of epidermis, 2-3 layers of endothecia, 1-2 layers of middle layers and 1 layer of tapetum. The middle layers soon break down after completion of microspore tetrads and the tapetum disappears before the pollen tetrads are fully mature. The epidermis and 2-3 layers of endothecia remain to the end. (3) Unlike those of longitudinal dehiscent anthers, the endothecia of Rhododendon× pulchrum are not fibrous at maturation. Instead, they are persistent and somewhat elastic through accumulation of polysaccharide granules in cells. (4) The four microspores produced by one microspore mother cell do not separate from each other and the pollens are released as tetrads, with viscous threads between pollens and among tetrads. The authors assume that the thickened multi-layer endothecia reduced the inner volume of the pollen sacs, therefore the pollen tetrads at the top are “squeezed out” from the dehiscence pore, and the viscous threads allow the pollen tetrads to be pulled out in clusters by pollinators.

The oil displacement technology of the water and gas dispersion system is a new enhanced oil recovery technology developed for low-permeability oilfields with low recoveries， which has obviously increased oil production in Changqing Oilfield. However， the effects among microbubbles in the dispersion system and pores are complex， and the research on its microscopic oil displacement mechanism is gradually deepening. According to the characteristics of heterogeneous low permeability core， a glass etching model with a side length of 1.5 cm was made， and the flow experiment of the CO2-water dispersion system was carried out under the conditions of reservoir temperature and pressure. The data such as bubble adsorption capacity， oil film pushing capacity， and bubble elastic energy were obtained by observing the interaction processes among microbubbles and oil， water， and rocks， and then the oil displacement effects were quantitatively characterized and analyzed. The experimental results show that the microbubble combines with the oil interface， to form a special oil adsorption film， which is significantly different from the mechanisms of water flooding and gas flooding. The merging of adjacent bubbles in the displacement process also promotes the convergence of oil films， and the merging of microbubbles helps the flow of bubbles so that the oil film adsorbed on the surface of the bubbles moves with the bubbles. The bubble volume expands due to the decrease in pressure， and the elastic energy released can promote the migration of the oil film adsorbed on the wall when the microbubble is transported. In addition， the oil film migration process of the microbubbles in the water and gas dispersion system was simulated and analyzed with the Volume of Fluid multiphase flow model， and the main factors that displace the oil film were obtained， which are the elastic energy generated by the deformation of the microbubbles and the energy of the microbubbles themselves. The energy of the bubble acts on the leading edge of the bubble and the bubble is pushed by contact with the surface of the oil film.

Snapshot spectral imaging technology enables the capture of complete spectral information of objects in an extremely short period of time, offering wide-ranging applications in fields requiring dynamic observations such as environmental monitoring, medical diagnostics, and industrial inspection. In the past decades, snapshot spectral imaging has made remarkable breakthroughs with the emergence of new computational theories and optical components. From the early days of using various spatial-spectral data mapping methods, they have evolved to later attempts to encode various dimensions of light, such as amplitude, phase, and wavelength, and then computationally reconstruct them. This review focuses on a systematic presentation of the system architecture and mathematical modeling of these snapshot spectral imaging techniques. In addition, the introduction of metasurfaces expands the modulation of spatial-spectral data and brings advantages such as system size reduction, which has become a research hotspot in recent years and is regarded as the key to the next-generation snapshot spectral imaging techniques. This paper provides a systematic overview of the applications of metasurfaces in snapshot spectral imaging and provides an outlook on future directions and research priorities.

In recent years, aerosols have been recognized as a prominent medium for the transmission of antibiotic-resistant bacteria and genes. Among these, particles with a particle size of 2 μm (PM2.5) can directly penetrate the alveoli. However, the presence of antibiotic-resistant genes in aerosols from pet hospitals and the potential risks posed by antibiotic-resistant bacteria in these aerosols to humans and animals need to be investigated. In this study, cefotaxime-resistant bacteria were collected from 5 representative pet hospitals in Changchun using a Six-Stage Andersen Cascade Impactor. The distribution of bacteria in each stage was analyzed, and bacteria from stage 5 and 6 were isolated and identified. Minimal inhibitory concentrations of isolates against 12 antimicrobials were determined using broth microdilution method. Quantitative Polymerase Chain Reaction was employed to detect resistance genes and mobile genetic elements that could facilitate resistance spread. The results indicated that ARBs were enriched in stage 5 (1.1–2.1 μm) and stage 3 (3.3–4.7 μm) of the sampler. A total of 159 isolates were collected from stage 5 and 6. Among these isolates, the genera Enterococcus spp. (51%), Staphylococcus spp. (19%), and Bacillus spp. (14%) were the most prevalent. The isolates exhibited the highest resistance to tetracycline and the lowest resistance to cefquinome. Furthermore, 56 (73%) isolates were multidrug-resistant. Quantitative PCR revealed the expression of 165 genes in these isolates, with mobile genetic elements showing the highest expression levels. In conclusion, PM2.5 from pet hospitals harbor a significant number of antibiotic-resistant bacteria and carry mobile genetic elements, posing a potential risk for alveolar infections and the dissemination of antibiotic resistance genes.

Abstract Environmental changes and ground subsidence along railway lines are serious concerns during high-speed railway operations. It is worth noting that AutoRegressive Integrated Moving Average (ARMA), Long Short-Term Memory (LSTM), and other prediction methods may present limitations when applied to predict InSAR time series results. To address this issue, this study proposes a prediction method that decomposes the nonlinear settlement time series of feature points obtained through InSAR technology using Ensemble Empirical Mode Decomposition (EEMD). Subsequently, multiple Intrinsic Mode Functions (IMFs) are generated, and each IMF is individually predicted using the Prophet forecasting model. Finally, we employ an equal-weight superimposition method to combine the results, resulting in the prediction of the InSAR settlement time series. The predicted values of each component are subsequently weighted equally and combined to derive the final prediction outcome. This paper selects InSAR monitoring data along a high-speed railway in inland China and uses the proposed method and ARMA and Prophet models to carry out comparative experiments. The experimental results show that compared with the ARMA and Prophet models, the method in this paper improves the root mean square error by 58.01% and 32.3%, and increases the mean absolute error by 62.69% and 33.78%, respectively. The predicted settlement values generated by our method exhibit better agreement with the actual InSAR monitoring values.

Gardenia fruit is a popular functional food and raw material for natural pigments. It comes from a wide range of sources, and different products sharing the same name are very common. Volatile organic compounds (VOCs) are important factors that affect the flavor and quality of gardenia fruit. This study used the Heracles NEO ultra-fast gas phase electronic nose with advanced odor analysis performance and high sensitivity to analyze six batches of gardenia fruit from different sources. This study analyzed the VOCs to find a way to quickly identify gardenia fruit. The results show that this method can accurately distinguish the odor characteristics of various gardenia fruit samples. The VOCs in gardenia fruit are mainly organic acid esters, ketones, and aldehyde compounds. By combining principal component analysis (PCA) and discriminant factor analysis (DFA), this study found that the hexanal content varied the most in different gardenia fruit samples. The VOCs allowed for the fruit samples to be grouped into two main categories. One fruit sample was quite different from the fruits of other origins. The results provide theoretical support for feasibility of rapid identification and quality control of gardenia fruit and related products in the future.

The optimization of explant selection and adjustment of plant growth regulators (PGRs) ratio may enhance the efficiency of micro-propagation of Gardenia jasminoides Ellis. The findings of the study suggest that the shoot tip proved to be the optimal explant for regenerating adventitious buds, with an impressive regeneration rate of 77.78% and the average number of adventitious buds being 2.86. The ideal medium consisted of Murashige and Skoog (MS) medium supplemented with 6-benzylaminopurine (6-BA) at a 2 mg L−1, indoleacetic acid (IAA) at a 0.2 mg L−1, kinetin (KT) at 0.15 mg L−1, resulting in an outstanding regeneration rate of adventitious buds reaching up to 91.11%. For rooting purposes, the best medium was found be half-strength MS supplemented with indoleacetic acid (IAA) 0.5 mg L−1, achieving an rate for adventitious roots amounting to as high as 97.78%. The culture plantlets ultimately thrived, achieving an impressive transplanting survival rate of 93.33%. The application of PGRs was also found to enhance the regeneration of adventitious buds by increasing the ratios of endogenous hormones ZR/IAA and GA3/IAA. Additionally, it facilitated the differentiation of adventitious roots by elevating the ratios of endogenous hormones IAA/ZR, IAA/GA3, and ABA/GA3. Our study would provide a theoretical reference for the establishment of an efficient gardenia tissue culture system and the industrial production of gardenia.

The compressibility of air, the uncertainty of dynamic models, and the existence of friction make pneumatic servo systems exhibit strong nonlinearity. Furthermore, the confluence of pneumatic-system nonlinearity and interference from the position system induces oscillations within the system, thereby posing a formidable challenge for achieving precise torque control. This study ensures precise torque control in a pneumatic actuator amid interference from the position system and proposes a novel active disturbance-rejection controller integrated with a Kalman filter. Firstly, in response to the oscillation stemming from the inherent nonlinearity of the pneumatic system and interference from the position system, this paper designs an active disturbance-rejection controller (ADRC) with robust anti-interference capabilities aimed at mitigating system oscillations. Secondly, to address the issue of sensor noise interfering with the ADRC and causing system oscillation, a first-order Kalman filter is designed to provide real-time and more accurate state estimation, effectively reducing oscillations and improving the robustness of the system. Finally, using the Lyapunov stability theory, the effectiveness of both the nonlinear extended observer and the convergence of the nonlinear error-state controller in the ADRC is proven. Experimental results indicate that the proposed controller reduces system oscillations and improves control accuracy.

The recovery of methane from low concentration coalbed methane can improve the utilization rate of coalbed methane, reduce the environmental pollution caused by gas emissions, and achieve the role of energy saving and emission reduction. In this paper, the recent research progress in hydrate separation of low concentration coalbed methane is analyzed, and the effects of thermodynamic promoters, kinetic promoters and mechanical strengthening are summarized respectively. Through the analysis, it is found that the effect of promoters needs to be further studied, and the appropriate promoters should be selected to find an effective way to promote the rapid synthesis of hydrate and help to promote the technical research on the separation and purification of low concentration coalbed methane by hydrate method.

Inchworms are a widely adopted bio-inspired model for soft crawling robots. Taking advantage of the good controllability of Shape Memory Alloy (SMA), this paper designs and manufactures an inchworm-inspired soft robot driven by SMA. Firstly, in the structural design, the paper compares the heat dissipation performance and driving efficiency of SMA actuators with two assembly forms: embedded and external to the silicone body. The external structure assembly design with superior performance is chosen. Secondly, in the analysis of the motion characteristics of the soft robot, a kinematic model is developed. Addressing the issue of inaccurate representation in traditional constitutive models due to difficult-to-measure parameters, such as martensite volume fraction, this paper derives an exclusive new constitutive model starting from traditional models using methods like the Taylor series and thermodynamic laws. The kinematic model is simulated using the Simulink platform to obtain its open-loop step response and sinusoidal signal response. Finally, an experimental platform is set up to conduct crawling tests on the soft robot in different planes. The experimental results show that the inchworm-inspired soft robot can perform continuous crawling motion, with a crawling speed of 0.041 mm/s on sandpaper under a constant current of 4A.

Delandistrogene moxeparvovec, an rAAVrh74-based gene transfer therapy designed to address absent functional dystrophin by delivering a transgene encoding an engineered micro-dystrophin, is approved in the US, UAE, Qatar, Kuwait, Bahrain, and Oman (March 2024) for ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed DMD mutation. Delandistrogene moxeparvovec showed stabilization of disease trajectory and manageable safety in patients aged ≥4–<8 years in a Phase 3 trial (EMBARK; NCT05096221). We report prespecified, exploratory analyses of muscle magnetic resonance (MR) data from EMBARK Part 1 (Week 52) to test the effect of delandistrogene moxeparvovec on muscle MR measures of disease progression. A subset of patients who received delandistrogene moxeparvovec (1.33×10¹⁴ vg/kg; n=19) or placebo (n=20) underwent quantitative muscle MR, including 8-point Dixon (MR imaging [MRI]) and proton MR spectroscopy (MRS) to measure muscle fat fraction (FF) and multi-slice spin echo imaging to measure transverse relaxation time (T₂). MRS FF was measured in the soleus and vastus lateralis, while MRI T₂ and FF were measured in 5 preselected leg muscles/groups with an important role in ambulation. A global statistical test (GST) combining all muscles and modalities assessed overall treatment effect. Overall, treated patients showed less disease progression vs. placebo. In all muscles, MRI FF and MRS FF magnitude of changes favored the treated group compared with placebo. The placebo group also showed increases (worsening) in T₂ (all muscles) compared with reductions (improvement) in treated patients (4/5 muscles; baseline to Week 52 change ranged from −1.05 to 0.05 msec [delandistrogene moxeparvovec] and 1.11 to 3.02 msec [placebo]). GST supports overall treatment benefit (P=0.0328). Muscle MRI changes were consistent with previously reported timed function tests, suggesting disease stabilization with delandistrogene moxeparvovec. [ABSTRACT FROM AUTHOR]

Delandistrogene moxeparvovec, an rAAVrh74-based gene transfer therapy (with a promoter containing a cardiac enhancer region) designed to address absent functional dystrophin by delivering a transgene encoding an engineered micro-dystrophin, is approved in the US, UAE, Qatar, Kuwait, Bahrain, and Oman (as of March 2024) for ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed DMD gene mutation. Delandistrogene moxeparvovec showed beneficial DMD disease trajectory modification and manageable safety in patients aged ≥4–<8 years in a Phase 3 trial (EMBARK; NCT05096221). We report results of a prespecified, exploratory analysis in patients who underwent non-contrast cardiac magnetic resonance imaging (cMRI) in EMBARK Part 1 (Week 52) to evaluate the effect of delandistrogene moxeparvovec on cardiac function, volume, and mass. A subset of patients who received delandistrogene moxeparvovec (1.33×10¹⁴ vg/kg; n=19) or placebo (n=20) underwent non-contrast cMRI at preselected sites per protocol. cMRI assessments included change from baseline to Week 52 in left ventricular filling volume, ejection fraction, mass, and global/segmental circumferential strain parameters. Myocardial tissue characterization was not assessed. At Week 52, analysis of cMRI left ventricular parameters, including end diastolic volume, ejection fraction, end systolic volume, and mass, revealed no relevant differences between delandistrogene moxeparvovec and placebo. Global circumferential strain of the left ventricle and analyses of segmental circumferential strain parameters across different regions of the left ventricle revealed no relevant differences between delandistrogene moxeparvovec and placebo. Treatment with delandistrogene moxeparvovec did not show any changes in cardiac function, volume, or mass as evaluated by non-contrast cMRI at Week 52 post-infusion. These data support the previously demonstrated manageable safety profile. [ABSTRACT FROM AUTHOR]

Delandistrogene moxeparvovec, an rAAVrh74-based gene transfer therapy designed to address absent functional dystrophin by delivering a transgene encoding engineered micro-dystrophin, is approved (US, UAE, Qatar, Kuwait, Bahrain, Oman; Mar 2024) for ambulatory pediatric patients (pts) aged 4 through 5 years (yrs) with Duchenne muscular dystrophy (DMD) with a confirmed DMD mutation. We report outcomes across 5 cohorts from the ENDEAVOR study (NCT04626674). Pts from Cohorts 1 (ambulatory; aged ≥4–<8 yrs), 2 (ambulatory; ≥8–<18 yrs), 3 (non-ambulatory), 4 (ambulatory; ≥3–<4 yrs) and 5 (mutations in DMD exons 1–17 [5a: ambulatory, ≥4–<9 yrs; 5b: non-ambulatory]) received single-dose intravenous delandistrogene moxeparvovec (1.33×10¹⁴ vg/kg [pts <70 kg] or 9.31×10¹⁵ vg total fixed dose [pts ≥70 kg]). Primary endpoint: change in micro-dystrophin expression from baseline to Week 12 by western blot. At time of infusion, pts were ambulatory (n=40) or non-ambulatory (n=8), aged 3.24–20.23 yrs and weighed 12.5–80.1 kg. The mean (SD) transduction at Week 12 was 2.93 (1.96) and 2.67 (0.92) vector genome copies per nucleus in ambulatory and non-ambulatory pts, respectively; mean (SD) delandistrogene moxeparvovec micro-dystrophin expression was 51.03% (46.95) and 40.06% (35.86), respectively. Overall, most common treatment-emergent adverse events (AEs) were vomiting (58.3%), nausea (47.9%), glutamate dehydrogenase increase (31.3%) and decreased appetite (31.3%); most were mild to moderate in severity. There were no deaths, study discontinuations or clinically relevant complement-mediated AEs. Mean transduction, expression and AEs experienced were comparable between ambulatory and non-ambulatory pts. The safety profile was manageable and consistent with the known population treated with delandistrogene moxeparvovec; no new safety concerns were observed in the broad ENDEAVOR population, including ambulatory and non-ambulatory pts, vs. the previously studied 4- to 7-yr pt population. [ABSTRACT FROM AUTHOR]

Background: Zellweger Syndrome (ZS), or cerebrohepatorenal syndrome, is a rare disorder due to PEX gene mutations affecting peroxisome function. While PEX6 coding mutations are known to cause ZS, the impact of noncoding mutations is less clear., Methods: A Chinese neonate and his family were subjected to whole exome sequencing (WES) and bioinformatics to assess variant pathogenicity. A minigene assay was also performed for detailed splicing variant analysis., Results: WES identified compound heterozygous PEX6 variants: c.315G>A (p. Trp105Ter) and c.2095-3 T>G. Minigene assays indicated that the latter variant led to abnormal mRNA splicing and the loss of exon 11 in PEX6 expression, potentially causing nonsense-mediated mRNA decay (NMD) or truncated protein structure., Conclusion: The study suggests that PEX6: c.2095-3 T>G might be a genetic contributor to the patient's condition, broadening the known mutation spectrum of PEX6. These insights lay groundwork for potential gene therapy for such variants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

P-type organic cathode materials typically exhibit high redox potentials and fast redox kinetics, presenting broad application prospects in aqueous zinc batteries (AZBs). However, most of the reported p-type organic cathode materials exhibit limited capacity (<100 mAh g -1 ), which is attributable to the low mass content ratio of oxidation-reduction active functional groups in these materials. Herein, we report a high-capacity p-type organic material, 5,12-dihydro-5,6,11,12-tetraazatetracene (DHTAT), for aqueous zinc batteries. Both experiments and calculation indicate the charge storage of DHTAT mainly involves the adsorption/desorption of ClO 4 - on the -NH- group. Benefitting from the high mass content ratio of the -NH- group in DHATA molecule, the DHATA electrode demonstrates a remarkable capacity of 224 mAh g -1 at a current density of 50 mA g -1 with a stable voltage of 1.12 V. Notably, after 5000 cycles at a high current density of 5 A g -1 , DHTAT retains 73 % of its initial capacity, showing a promising cycling stability. In addition, DHTAT also has good low-temperature performance and can stably cycle at -40 °C for 4000 cycles at 1 A g -1 , making it a competitive candidates cathode material for low-temperature batteries., (© 2024 Wiley-VCH GmbH.)

Purpose: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME., Methods: This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS)., Results: Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group)., Conclusion: This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.

The application of machine learning (ML) techniques in the lithium battery field is relatively new and holds great potential for discovering new materials, optimizing electrochemical processes, and predicting battery life. However, the accuracy of ML predictions is strongly dependent on the underlying data, while the data of lithium battery materials faces many challenges, such as the multi-sources, heterogeneity, high-dimensionality, and small-sample size. Through the systematic review of the existing literatures, several effective strategies are proposed for data processing as follows: classification and extraction, screening and exploration, dimensionality reduction and generation, modeling and evaluation, and incorporation of domain knowledge, with the aim to enhance the data quality, model reliability, and interpretability. Furthermore, other possible strategies for addressing data quality such as database management techniques and data analysis methodologies are also emphasized. At last, an outlook of ML development for data processing methods is presented. These methodologies are not only applicable to the data of lithium battery materials, but also endow important reference significance to electrocatalysis, electrochemical corrosion, high-entropy alloys, and other fields with similar data challenges., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Establishing urban greenspaces is an effective approach for improving urban air quality and thermal environments. However, at a finer scale, the potential mechanisms of urban greenspaces providing pollution retention and cooling benefits remain unclear, especially for the three-dimensional structural characteristics of plant communities. To explore the potential mechanisms, we conducted field experiments on 108 plant communities in Beijing and simultaneously monitored PM 10 concentration data and meteorological data both within and outside the plant communities. We analyzed the relationships between three-dimensional structural characteristic factors, the pollution retention benefit, and the cooling benefit. The results indicated that the majority of the plant communities (90.91%) can simultaneously provide both benefits. The herbaceous layer was a crucial factor influencing the pollution retention benefit, with a nonlinear positive correlation between the pollution retention benefit and the ratio of three-dimensional green biomass of herbs and trees (RTDGB-HT) and a threshold of 0.80-1.00. The tree layer was a crucial factor influencing the cooling benefit, as indicated by a positive linear correlation between the cooling benefit and the ratio of three-dimensional green biomass of trees (RTDGB-T). With changes in three-dimensional structural characteristic factors, the rate of change in pollution retention benefit factors was 3-5.5 times that in cooling benefit factors. Mediation analysis confirmed the trade-off between the pollution retention and cooling benefits, with trees indirectly enhancing pollution retention benefit by reducing the daily mean temperature reduction rate (R-T mean ) by 20.44-22.27% and by reducing the daily maximum temperature reduction rate (R-T max ) by 13.14-15.99%. Overall, 13-23% of the pollution retention benefit was achieved through reducing cooling benefit, and interventions involving extreme heat can minimize the trade-off between the pollution retention and cooling benefits compared to reducing cooling benefit throughout the day. Our findings enrich and extend the current understanding of the correlations associated with the comprehensive benefits at the plant community scale, emphasizing the differences in three-dimensional structural characteristics that provide different benefits, which can better inform the development of refined and scientifically managed strategies for green space renovation., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Automatic and accurate tooth segmentation on 3D dental point clouds plays a pivotal role in computer-aided dentistry. Existing Transformer-based methods focus on aggregating local features, but fail to directly model global contexts due to memory limitations and high computational cost. In this paper, we propose a novel Transformer-based 3D tooth segmentation network, called PointRegion, which can process the entire point cloud at a low cost. Following a novel modeling of semantic segmentation that interprets the point cloud as a tessellation of learnable regions, we first design a RegionPartition module to partition the 3D point cloud into a certain number of regions and project these regions as embeddings in an effective way. Then, an offset-attention based RegionEncoder module is applied on all region embeddings to model global context among regions and predict the class logits for each region. Considering the irregularity and disorder of 3D point cloud data, a novel mechanism is proposed to build the point-to-region association to replace traditional convolutional operations. The mechanism, as a medium between points and regions, automatically learns the probabilities that each point belongs to its neighboring regions from the similarity between point and region features, achieving the goal of point-level segmentation. Since the number of regions is far less than the number of points, our proposed PointRegion model can leverage the capability of the global-based Transformer on large-scale point clouds with low computational cost and memory consumption. Finally, extensive experiments demonstrate the effectiveness and superiority of our method on our dental dataset., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background and Purpose: Clinicians use the CTCAE scale to grade radiation dermatitis (RD) based on edema, erythema, and desquamation. The purpose of this study was to correlate the CTCAE scores with the severity of patient-reported symptoms using a skin symptom assessment (SSA) and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS)., Materials and Methods: This is a secondary analysis of a randomized controlled trial involving 376 patients receiving Mepitel Film or standard-of-care for RD prophylaxis. The highest symptom categories for SSA and patient-component RISRAS assessments were selected from all time points, and a summary analysis and Spearman correlation coefficient was calculated for patients with CTCAE Grades 0, 1, 2, 3, and Grade 2/3, respectively. Analyses were conducted across all patients, within each treatment arm, and between arms in patients with only Grade 2 or 3 toxicity., Results: Weak correlations between CTCAE scores and all patient-reported skin symptoms were found across the entire cohort and each treatment arm (p < 0.05). Patients with Grade 2 (n = 72) and Grade 3 RD (n = 24) reported similar rates of patient-reported moderate-to-severe skin symptoms (11-72% vs 14-79%), with no significant difference in rates of individual moderate-to-severe symptom between these cohorts (p > 0.05). Between treatment arms, rates of patient-reported moderate-to-severe scores were similar for most symptoms., Conclusion: CTCAE RD scores are weakly correlated with patient-reported skin symptoms and cannot distinguish between patients with severe patient-reported outcomes. Clinicians should consider the limitations of CTCAE grading and incorporate patient-reported outcomes within clinical practice., Competing Interests: Declarations Ethics approval This research was conducted in accordance with the Declaration of Helsinki. Human ethics and consent to participate declarations were not applicable. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Toward high-density single atom catalysts (SACs), the interaction between neighboring SACs and the induced non-linear loading effect become crucial for their intrinsic catalytic performance. Despite recent investigations on homonuclear SACs, understanding such effect in heteronuclear SACs remains limited. Using Fe and Co SACs co-supported on the nitrogen-doped graphene as a model system, the loading effect on the site-specific activity of heteronuclear SACs toward oxygen reduction reaction (ORR) is here reported by density functional theory calculations. The Fe site exhibits an oscillatory decrease in activity with the loading. In contrast, the Co site has a volcano-like activity with the optimum performance achieved at ≈16.8 wt.% (average inter-site distance: ≈7 Å). At the ultra-high loading of 38.4 wt.% (inter-site distance: ≈4 Å), the Co site is the only ORR active site, whereas Fe sites turn into spectators. This distinct loading-dependent activity between the Fe and Co sites can be ascribed to their difference in the binding capability with the substrate and the d xz  and d yz orbitals' occupation. These findings highlight the importance of the loading effect in heteronuclear SACs, which could be useful for the development of high-performance heteronuclear and high-entropy SACs toward various catalytic reactions in the high-loading regime., (© 2024 Wiley‐VCH GmbH.)

The addition of active ingredients such as antibacterial agent and non-active ingredients such as plastic microspheres (MPs) in personal care products (PCPs) are the common pollutants in the aquatic environment, and their coexistence poses potential threat to the aquatic ecosystem. As a substitute for the traditional antibacterial ingredients triclosan and triclocarban, the usage of parachlormetaxylenol (PCMX) is on the rise and is widely used in PCPs. In this study, the adsorption and desorption behaviors of PCMX were investigated with two typical MPs, polyvinyl chloride (PVC) and polyethylene (PE), and the effects of different aging modes and molecular mechanisms were explored through batch experiments and density functional theory calculation. Both laboratory aging and field aging resulted in surface wrinkles of MPs, along with an increased proportion of oxygen-containing functional groups (CO, -OH). At the same aging time, the degree of laboratory aging was stronger than that of field aging, and the aging degree of PVC was greater that of PE. The aging process enhanced the adsorption capacity of MPs for PCMX. The equilibrium adsorption capacity of PVC increased from 3.713 mg/g (virgin) to 3.823 mg/g (field aging) and 3.969 mg/g (laboratory aging), while that of PE increased from 3.509 mg/g to 3.879 mg/g and 4.109 mg/g, respectively. Meanwhile, aging also resulted in an increase in the desorption capacity of PCMX from PVC and PE. Oxygen-containing functional groups in aged MPs could serve as adsorption sites for PCMX and improved the electrostatic adsorption capacity. Oxygen-containing groups generated on the surface of aged MPs formed hydrogen bonding with the phenolic hydroxyl groups of PCMX, which became the main driving force for adsorption. Our results reveal the potential impact and mechanism of aging on the adsorption of PCMX by MPs, which provides new insights for the interaction mechanism between environmental MPs and associated contaminants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Carbon-doped nitrogen clusters have represented a fascinating area of materials science in recent years. However, achieving precise control of the doping level and distribution of carbon within nitrogen clusters is challenging. Advanced techniques are required to elucidate their exact structures and electronic properties. Here, we perform systematic structure searches of anionic carbon-doped nitrogen clusters by the Crystal structure AnaLYsis by Particle Swarm Optimization method combined with density-functional theory calculations. The ground state structures of CN n - ( n = 4-16) clusters for each cluster size are determined. The structural evolution, photoelectron energy spectra, electronic properties, and chemical bonding modes of anionic CN n - ( n = 4-16) clusters are discussed. The calculated results indicate that the two-dimensional planar geometry of the anionic CN 6 - cluster with the C 1 symmetry exhibits robust stability. The molecular orbitals and the adaptive natural density partitioning calculations show that the high stability of the anionic CN 6 - cluster is attributed to the localized σ-bonding formed by the 2p orbitals of carbon and nitrogen atoms. The four delocalized π chemical bonds contribute to the stability of the anionic CN 6 - cluster, resulting in a stable ring geometry. The present results enrich the database of geometric structures of carbon-nitrogen clusters and provide valuable insights for the experimental synthesis and characterization of nitrogen-based clusters.

Hydroxylamine, as an important reducing agent, disinfectant, foaming agent, and biocide, plays a role in both human life and industrial production. However, its synthesis is confronted with challenges, such as high pollution and large consumption. Here, we propose a coordination tailoring strategy to design 47 graphene-supported single iron atom catalysts (SACs), namely, Fe@C x Z y (Z = B, N, O, P, and S), for the reduction of nitric oxide to hydroxylamine. Using density functional theory calculations, we demonstrated the great impact of the coordination environment on the stability, catalytic selectivity, and activity of the Fe site. We identified that the experimentally available Fe@N 4 possesses an ultralow theoretical limiting potential of -0.32 V compared to that of other catalysts. A comprehensive investigation of the electronic properties elucidates the underlying active origin and reaction mechanism of the nitric oxide reduction reaction to hydroxylamine on Fe@N 4 . These results not only explain the catalytic origin of synthesized SACs for the NH 2 OH production but also offer theoretical guidance for further optimizing high-performance catalysts.

High ammonia concentration inhibits archaea's activity, causing the accumulation of H 2 and acetate, which suppresses methane production in anaerobic digestion (AD). The study aimed to enhance microbial hydrogen metabolism through a side-stream hydrogen domestication (SHD) strategy, which involves applying hydrogen stimulation to a portion of the sludge separately. SHD maintained a stable methane yield of 407.5 mL/g VS at a high total ammonia nitrogen (TAN) concentration of 3.1 g/L. In contrast, the control group gradually decreased and stopped methane production at a TAN concentration of 2.3 g/L. Further analysis using enzyme activity assays, flow cytometry, and metagenomics explored the mechanisms underlying ammonia tolerance of SHD-treated group. SHD reshaped the microbial community, enriching homoacetogens and Methanosaeta-dominated methanogenic archaea. Key metabolic pathways including homoacetogenesis, butyrate degradation, propionate degradation, and methane production were enhanced. The activity of related enzymes also increased. Gene abundance in energy-generating pathways, such as glycolysis, was enhanced, ensuring adequate ATP production. Additionally, the high gene abundance of ion transport systems contributed to regulating proton imbalance and supplementing intracellular K + . This study provides important insights and practical guidance for developing novel techniques in the field of anaerobic digestion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this paper and all authors have seen and approved the final version of the manuscript. They warrant that the article is the authors’ original work, has not been published prior and is not under consideration for publication elsewhere., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Laparoscopic surgery is increasingly used for rectal cancer, but the long-term oncological outcomes for low rectal cancer have not been fully established. We aimed to evaluate the 3-year survival outcomes of laparoscopic surgery versus open surgery in the treatment of low rectal cancer., Methods: This multicentre, randomised, controlled, non-inferiority trial was conducted at 22 tertiary hospitals in China. Individuals aged 18-75 years with histologically confirmed cT1-2N0, cT3-4aN0, or cT1-4aN1-2 rectal adenocarcinoma within 5 cm from the dentate line were eligible for inclusion. Participants were randomly assigned (2:1) to undergo laparoscopic surgery or open surgery. Central randomisation was conducted using a web response system, and was stratified by clinical stage, age, sex, BMI, and American Society of Anesthesiologists classification. Investigators, patients and statisticians were not masked to group allocation. The primary outcome was 3-year disease-free survival, defined as the time from the date of surgery to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first. Non-inferiority was defined as a lower limit of one-sided 97·5% CI for group difference (laparoscopic surgery group minus open surgery group) of greater than -10%. The primary analyses were performed in the modified intention-to-treat population, which excluded patients with distant metastasis discovered during surgery and those who did not undergo surgery or underwent local resection only. The trial is registered with ClinicalTrials.gov, NCT01899547, and has been completed., Findings: Between Nov 12, 2013, and June 6, 2018, 1070 patients were enrolled and randomly assigned to treatment. 1039 patients (685 in the laparoscopic surgery group and 354 in the open surgery group; median age 57 years, IQR 50 to 64; 620 [60%] male and 419 [40%] women) were included in the modified intention-to-treat analysis. 3-year disease-free survival was 81·4% (95% CI 78·2 to 84·1) in the laparoscopic surgery group and 79·8% (75·2 to 83·6) in the open surgery group (hazard ratio [HR] 0·92, 95% CI 0·69 to 1·23; p=0·56). The difference between groups was 1·60% (one-sided 97·5% CI -3·34 to ∞, p<0·0001 for non-inferiority). 3-year overall survival was 91·7% (95% CI 89·3 to 93·5) in the laparoscopic surgery group and 93·7% (90·6 to 95·8) in the open surgery group (HR 1·34, 95% CI 0·82 to 2·19; p=0·24). 3-year locoregional recurrence was 3·7% (95% CI 2·5 to 5·3) and 2·3% (1·1 to 4·3), respectively (HR 1·64, 95% CI 0·74 to 3·63; p=0·22). 5-year overall survival was 84·6% (95% CI 81·5 to 87·1) and 86·6% (82·5 to 89·8) in the open group (HR 1·16, 95% CI 0·82 to 1·64; p=0·41)., Interpretation: Laparoscopic surgery performed by experienced surgeons is non-inferior to open surgery for 3-year disease-free survival among patients with low rectal cancer. These results support the use of laparoscopic surgery for low rectal cancer., Funding: The Key Clinical Specialty Discipline Construction Program of the National Health and Family Planning Commission of China; Minimally Invasive Medical Center Construction Program, Fujian Province, China; and Joint Funds for the Innovation of Science and Technology, Fujian Province, China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Peripheral T cell lymphomas (PTCLs) are prototypical epigenetic malignancies with invariably poor prognoses. Novel and effective therapeutic strategies are needed to improve clinical outcomes, particularly in relapsed/refractory patients., Methods: We conducted a multicenter phase 2 study to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory PTCLs (registration number: ChiCTR2000037232). The primary endpoint was the best overall response rate., Findings: As of May 1st, 2024, thirty patients were evaluable for efficacy and toxicity. The best overall response rate was 53.3%, meeting its primary endpoint. Among the patients with angioimmunoblastic T cell lymphoma (AITL; N = 19), a numerically higher response rate was observed, regardless of whether chemotherapy was combined, compared to patients with non-AITL. After a median follow-up of 36.6 months, median progression-free survival and overall survival were 7.1 and 8.7 months, respectively. Patients with AITL who received combination chemotherapy (N = 12) achieved the most promising response rates (overall response rate, 91.7%; complete remission rate, 66.7%) and survival outcomes (median progression-free survival, 17.2 months; median overall survival, 38.8 months). The most common grade 3-4 toxicities were neutropenia (40.0%) and thrombocytopenia (30.0%)., Conclusions: The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with relapsed/refractory PTCLs. Patients with AITL, in particular, may benefit more from this combination treatment and should be the focus of future studies., Funding: This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Equecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary., Objective: To evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion., Design, Setting, and Participants: The FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. As of September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022., Interventions: Patients received a single infusion of eque-cel at 1.0 × 106 CAR-positive T cells/kg after the lymphodepletion., Main Outcomes and Measures: Efficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives., Results: Of 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10-5. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell-associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell-associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days., Conclusions and Relevance: In this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000033946.

Introduction: Alanyl-glutamine (Ala-Gln) is a compound known for its protective effects in various tissue injuries. However, its role in asthma-related lung injuries remains underexplored. This study investigates the mechanisms by which Ala-Gln modulates sDPP4-induced airway epithelial-mesenchymal transition and ovalbumin (OVA)-induced asthma in a mouse model., Methods: An asthma model was established in female C57BL/6 J mice by using OVA. CD4+ T cells and bronchial epithelial cells (BECs) were isolated from the spleen and bronchi of the mice, respectively. Interventions included recombinant sCD26/sDPP4 protein, Ala-Gln, and EX527 (a SIRT1 inhibitor). Flow cytometry was used to assess Th17 and Treg cell populations. Mice were treated with Ala-Gln, EX527, and budesonide (BUD). Histopathological changes in lung tissues were evaluated using hematoxylin-eosin and Masson staining. White blood cell counts were measured with a hematology analyzer. The expression levels of DPP4, IL-17, SIRT1, SMAD2/3, N-cadherin, E-cadherin, MMP9, and α-SMA proteins were analyzed., Results: Treatment with recombinant sCD26/sDPP4 resulted in decreased E-cadherin expression in BECs and increased levels of α-SMA, MMP9, and N-cadherin, effects that were mitigated by Ala-Gln. Ala-Gln also prevented the reduction in SIRT1 expression in BECs and the increase in Th17 cell differentiation induced by recombinant sCD26/sDPP4. EX527 administration alongside Ala-Gln reversed these changes and enhanced the phosphorylation of SMAD2/3 through SIRT1 signaling. BUD alone reduced inflammation and fibrosis in bronchial tissue and lowered the Th17/Treg ratio in peribronchial lymph nodes. The therapeutic effect of BUD was further improved with concurrent Ala-Gln treatment., Conclusion: Ala-Gln can inhibit BEC fibrosis and Th17 cell differentiation mediated by recombinant sCD26/sDPP4 through the SIRT1 pathway. Combined with BUD, Ala-Gln enhanced therapeutic efficacy in OVA-induced asthma in mice, which could offer improved outcomes for asthmatic patients with elevated DPP4 levels., (© 2024 S. Karger AG, Basel.)

Liver fibrosis, mainly arising from chronic viral or metabolic liver diseases, is a significant global health concern. There is currently only one FDA-approved drug (Resmetirom) in the market to combat liver fibrosis. Both galectin-3 and epidermal growth factor receptor (EGFR) play important roles in liver fibrosis, while galectin-3 may interact with EGFR. Galectin-3 inhibitors, typically lactose or galactose derivatives may inhibit liver fibrosis. We hypothesized that targeting both galectin-3 and EGFR may have better effect against liver fibrosis. Here, EGFR inhibitor erlotinib was used in a series of designed galectin-3 inhibitors after hybridization with the pharmacophore structure in reported galectin-3 inhibitors to impede hepatic stellate cells (HSCs) activation by a typical method of click chemistry. Bioactivity test results showed that compound 29 suppressed TGF-β-induced upregulation of fibrotic markers (α-SMA, fibronectin-1, and collagen I). The preferred compound 29 displayed better binding to galectin-3 (KD = 52.29 μM) and EGFR protein (KD = 3.31 μM) by SPR assay. Further docking studies were performed to clarify the possible binding mode of compound 29 with galectin-3 and EGFR. Taken together, these results suggested that compound 29 could be a potential dual galectin-3 and EGFR inhibitor as leading compound for anti-liver fibrosis new drug development., (© 2024 Wiley‐VCH GmbH.)

Background and Purpose: The study evaluated the concordance between patient-reported outcomes (PRO) and clinician-reported outcomes (CRO) of acute radiation dermatitis (RD) symptoms following adjuvant radiotherapy for early-stage and locally advanced breast cancer., Material and Methods: This is a secondary analysis of a multi-center randomized phase 3 trial (376 patients). Ordinal logistic regression analysis was used to compare the Skin Symptom Assessment (SSA) independently reported by both patients and clinicians. Concordance between patient- and clinician-reported SSAs for RD symptoms was measured by percent concordance, concordance index (C-statistic), and Cohen's Kappa. Analyses were performed across all patients in the original modified intention-to-treat analysis and those with only grade 2-3 (CTCAE) RD., Results: PROs were significantly more severe than CROs across all RD symptoms (Odds Ratio [OR] > 1; p < 0.0001). Pigmentation (OR 5.4), blistering/peeling (OR 4.0), and pain/soreness (OR 3.9) were the most differentially reported symptoms. Poor-to-low concordance was noted between patient- and clinician-reported SSAs for all RD symptoms for the entire cohort (percent concordance < 50%, C-statistic 0.52-0.63, Cohen's Kappa 13.9-23.4%) and those with grade 2-3 RD (percent concordance < 50%, C-statistic 0.56-0.66, Cohen's Kappa 2.0-24.5%). Similarly, poor-to-low concordance was noted in both Mepitel film and standard-of-care arms., Conclusion: PROs and CROs have poor concordance in breast RD, and patients report worse outcomes than clinicians, regardless of RD severity or prophylaxis. PROs must be further integrated into routine clinical practice and clinical trial design to reduce the risk of underreporting symptoms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)