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Abstract During the wound healing process, the activation of signal transducer and activator of transcription 3 (STAT3) is considered crucial for the migration and proliferation of epithelial cells, as well as for establishing the inflammatory environment. However, an excessive STAT3 activation aggravates scar formation. Here we show that 450 nm blue light and 630 nm red light can differentially regulate the phosphorylation of STAT3 (p-STAT3) and its downstream cytokines in keratinocytes. Further mechanistic studies reveal that red light promotes wound healing by activating the PI3 kinase p110 beta (PI3Kβ)/STAT3 signaling axis, while blue light inhibits p-STAT3 at the wound site by modulating cytochrome c-P450 (CYT-P450) activity and reactive oxygen species (ROS) generation. In a mouse scar model, skin wound healing can be significantly accelerated with red light followed by blue light to reduce scar formation. In summary, our study presents a potential strategy for regulating epithelial cell p-STAT3 through visible light to address skin scarring issues and elucidates the underlying mechanisms.

Abstract NASICON (Na $$_{1+x}$$ 1 + x Zr $$_2$$ 2 Si $$_x$$ x P $$_{3-x}$$ 3 - x O $$_{12}$$ 12 ) is a well-established solid-state electrolyte, renowned for its high ionic conductivity and excellent chemical stability, rendering it a promising candidate for solid-state batteries. However, the intricate influence of ion doping on their performance has been a central focus of research, with existing studies often lacking comprehensive evaluation methods. This study introduces a deep-learning-based approach to efficiently evaluate ion-doped NASICON materials. We developed a convolutional neural network (CNN) model capable of predicting the performance of various ion-doped NASICON compounds by leveraging extensive datasets from prior experimental investigation. The model demonstrated high accuracy and efficiency in predicting ionic conductivity and electrochemical properties. Key findings include the successful synthesis and validation of three NASICON materials predicted by the model, with experimental results closely matching the model’s predictions. This research not only enhances the understanding of ion-doping effects in NASICON materials but also establishes a robust framework for material design and practical applications. It bridges the gap between theoretical predictions and experimental validations. Graphical Abstract

Abstract Accumulated data implicate that long noncoding RNA (lncRNA) plays a pivotal role in rheumatoid arthritis (RA), potentially serving as a competitive endogenous RNA (ceRNA) for microRNAs (miRNAs). The lncRNA myocardial infarction-associated transcript (MIAT) has been demonstrated to regulate inflammation. However, the role of MIAT in the inflammation of RA remains inadequately explored. This study aims to elucidate MIAT’s role in the inflammation of lipopolysaccharide (LPS)-induced macrophages and to uncover the underlying molecular mechanisms. We observed heightened MIAT expression in LPS-induced J774A.1 cells and collagen-induced arthritis mouse models, in contrast to the expression pattern of miR-30a-5p. Silencing MIAT resulted in increased expression of the inflammatory cytokines IL-1β and TNF-α. Simultaneously, MIAT interference significantly impeded macrophage autophagy, evidenced by decreased expression of autophagy-related markers LC3-II and Beclin-1, alongside increased levels of p62 in LPS-induced J774A.1 cells. Notably, MIAT functioned as a ceRNA, sponging miR-30a-5p and exerting a negative regulatory influence on its expression. SOCS1 emerged as a target of miR-30a-5p, modulated by MIAT. Mechanistically, inhibiting miR-30a-5p reversed the impact of MIAT deficiency in promoting LPS-induced inflammation, while SOCS1 knockdown countered the cytokine inhibitory effect induced by silencing miR-30a-5p. In summary, this study indicates that lncRNA MIAT suppresses inflammation in LPS-induced J774A.1 macrophages by stimulating autophagy through the miR-30a-5p/SOCS1 axis. This suggests that MIAT holds promise as a potential therapeutic target for RA inflammation.

Abstract To the best of our knowledge, N6-Methyladenosine (m6A) exerts a significant role in the occurrence and development of various tumors. Gastric cancer (GC), originating from the mucosal epithelium in the digestive tract, is the fifth most common cancer and the third most common cause of cancer death around the world. Therefore, it is urgent to explore the specific mechanism of tumorigenesis of GC. As we all know, m6A modification as the most common RNA modification, is involved in the modification of mRNA and ncRNA at the post-transcriptional level, which played a regulatory role in various biological processes. As identified by numerous studies, the m6A modification are able to influence the proliferation, apoptosis, migration, and invasion of GC. What’s more, m6A modification are associated with EMT, drug resistance, and aerobic glycolysis in GC. m6A related-ncRNAs may be a valuable biomarker used by the prediction of GC diagnosis in the future. This review summarizes the role of m6A modification in the mechanism of gastric cancer, with the aim of identifying biological progress.

Summary: Spindle oscillation is a waxing-and-waning neural oscillation observed in the brain, initiated at the thalamic reticular nucleus (TRN) and typically occurring at 7–15 Hz. Experiments have shown that in the adult brain, electrical synapses, rather than chemical synapses, dominate between TRN neurons, suggesting that the traditional view of spindle generation via chemical synapses may need reconsideration. Based on known experimental data, we develop a computational model of the TRN network, where heterogeneous neurons are connected by electrical synapses. The model shows that the interplay between synchronizing electrical synapses and desynchronizing heterogeneity leads to multiple synchronized clusters with slightly different oscillation frequencies whose summed-up activity produces spindle oscillation as seen in local field potentials. Our results suggest that during spindle oscillation, the network operates at the critical state, which is known for facilitating efficient information processing. This study provides insights into the underlying mechanism of spindle oscillation and its functional significance.

Background: Delayed post-hypoxic leukoencephalopathy (DPHL) is characterized by a biphasic clinical course, with complete recovery from coma to a fully conscious state lasting one to four weeks (lucid interval), followed by abrupt neurological deterioration as an indirect consequence of hypoxic events like carbon monoxide poisoning and narcotic drug overdose. To our best knowledge, there are no documented cases in literature of choreoathetosis and dementia following poppy-induced DPHL with 14-3-3 protein in cerebrospinal fluid (CSF). Case presentation: We report the case of a 70-year-old female who underwent cardiopulmonary resuscitation (CPR) due to overdose of homemade refined opium poppy paste two weeks prior to presentation. She presented a progressive cognitive decline, along with the development of apraxia and choreic movement affecting her tongue and bilateral upper and lower extremities. During the symptomatic phase, brain magnetic resonance imaging (MRI) showed bilateral symmetrical hyperintense signals mostly in central frontal, temporal, and parieto-occipital lobes in the diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences which are the characteristic findings of DPHL. CSF routine analysis, as well as toxicology screening, autoimmune and paraneoplastic encephalitis panels were negative, but the presence of 14-3-3 protein in the CSF was detected. With steroid therapy, hyperbaric oxygen therapy and symptomatic treatment, she experienced gradual improvement in cognition, motivation, and psychomotor function. Conclusion: DPHL represents a distinct form of encephalopathy characterized by unique clinical course and imaging features. It is the first report of DPHL with positive 14-3-3 protein in CSF. The potential of 14-3-3 protein as a biomarker for diagnosing DPHL and its ability to predict disease severity and prognosis warrants further research.

We synthesized the ferromagnetic EuAgP semiconductor and conducted a comprehensive study of its crystalline, magnetic, heat capacity, band gap, and magnetoresistance properties. Our investigation utilized a combination of X-ray diffraction, optical, and PPMS DynaCool measurements. EuAgP adopts a hexagonal structure with the P63/mmc space group. As the temperature decreases, it undergoes a magnetic phase transition from high-temperature paramagnetism to low-temperature ferromagnetism. We determined the ferromagnetic transition temperature to be TC = 16.45(1) K by fitting the measured magnetic susceptibility using a Curie-Weiss law. Heat capacity analysis of EuAgP considered contributions from electrons, phonons, and magnons, revealing η = 0.03 J/(mol·K2), indicative of semiconducting behavior. Additionally, we calculated a band gap of ∼1.324(4) eV based on absorption spectrum measurements. The resistivity versus temperature of EuAgP measured in the absence of an applied magnetic field shows a pronounced peak around TC, which diminishes rapidly with increasing applied magnetic fields, ranging from 1 to 14 T. An intriguing phenomenon emerges in the form of a distinct magnetoresistance transition, shifting from positive (e.g., 1.95% at 300 K and 14 T) to negative (e.g., −30.73% at 14.25 K and 14 T) as the temperature decreases. This behavior could be attributed to spin-disordered scattering.

ABSTRACTOvarian aging occurs prior to the aging of other organ systems and acts as the pacemaker of the aging process of multiple organs. As life expectancy has increased, preventing ovarian aging has become an essential goal for promoting extended reproductive function and improving bone and genitourinary conditions related to ovarian aging in women. An improved understanding of ovarian aging may ultimately provide tools for the prediction and mitigation of this process. Recent studies have suggested a connection between ovarian aging and the gut microbiota, and alterations in the composition and functional profile of the gut microbiota have profound consequences on ovarian function. The interaction between the gut microbiota and the ovaries is bidirectional. In this review, we examine current knowledge on ovary-gut microbiota crosstalk and further discuss the potential role of gut microbiota in anti-aging interventions. Microbiota-based manipulation is an appealing approach that may offer new therapeutic strategies to delay or reverse ovarian aging.

Hippocampal place cells in freely moving rodents display both theta phase precession and procession, which is thought to play important roles in cognition, but the neural mechanism for producing theta phase shift remains largely unknown. Here, we show that firing rate adaptation within a continuous attractor neural network causes the neural activity bump to oscillate around the external input, resembling theta sweeps of decoded position during locomotion. These forward and backward sweeps naturally account for theta phase precession and procession of individual neurons, respectively. By tuning the adaptation strength, our model explains the difference between ‘bimodal cells’ showing interleaved phase precession and procession, and ‘unimodal cells’ in which phase precession predominates. Our model also explains the constant cycling of theta sweeps along different arms in a T-maze environment, the speed modulation of place cells’ firing frequency, and the continued phase shift after transient silencing of the hippocampus. We hope that this study will aid an understanding of the neural mechanism supporting theta phase coding in the brain.

Abstract Conventional circuit elements are constrained by limitations in area and power efficiency at processing physical signals. Recently, researchers have delved into high-order dynamics and coupled oscillation dynamics utilizing Mott devices, revealing potent nonlinear computing capabilities. However, the intricate yet manageable population dynamics of multiple artificial sensory neurons with spatiotemporal coupling remain unexplored. Here, we present an experimental hardware demonstration featuring a capacitance-coupled VO2 phase-change oscillatory network. This network serves as a continuous-time dynamic system for sensory pre-processing and encodes information in phase differences. Besides, a decision-making module for special post-processing through software simulation is designed to complete a bio-inspired dynamic sensory system. Our experiments provide compelling evidence that this transistor-free coupling network excels in sensory processing tasks such as touch recognition and gesture recognition, achieving significant advantages of fewer devices and lower energy-delay-product compared to conventional methods. This work paves the way towards an efficient and compact neuromorphic sensory system based on nano-scale nonlinear dynamics.

Abstract Background Epigenetic factors influence the odontogenic differentiation of dental pulp stem cells and play indispensable roles during tooth development. Some microRNAs can epigenetically regulate other epigenetic factors like DNA methyltransferases and histone modification enzymes, functioning as epigenetic-microRNAs. In our previous study, microarray analysis suggested microRNA-93-5p (miR-93-5p) was differentially expressed during the bell stage in human tooth germ. Prediction tools indicated that miR-93-5p may target lysine-specific demethylase 6B (KDM6B). Therefore, we explored the role of miR-93-5p as an epi-miRNA in tooth development and further investigated the underlying mechanisms of miR-93-5p in regulating odontogenic differentiation and dentin formation. Methods The expression pattern of miR-93-5p and KDM6B of dental pulp stem cells (DPSCs) was examined during tooth development and odontogenic differentiation. Dual luciferase reporter and ChIP-qPCR assay were used to validate the target and downstream regulatory genes of miR-93-5p in human DPSCs (hDPSCs). Histological analyses and qPCR assays were conducted for investigating the effects of miR-93-5p mimic and inhibitor on odontogenic differentiation of hDPSCs. A pulpotomy rat model was further established, microCT and histological analyses were performed to explore the effects of KDM6B-overexpression and miR-93-5p inhibition on the formation of tertiary dentin. Results The expression level of miR-93-5p decreased as odontoblast differentiated, in parallel with elevated expression of histone demethylase KDM6B. In hDPSCs, miR-93-5p overexpression inhibited the odontogenic differentiation and vice versa. MiR-93-5p targeted 3′ untranslated region (UTR) of KDM6B, thereby inhibiting its protein translation. Furthermore, KDM6B bound the promoter region of BMP2 to demethylate H3K27me3 marks and thus upregulated BMP2 transcription. In the rat pulpotomy model, KDM6B-overexpression or miR-93-5p inhibition suppressed H3K27me3 level in DPSCs and consequently promoted the formation of tertiary dentin. Conclusions MiR-93-5p targets epigenetic regulator KDM6B and regulates H3K27me3 marks on BMP2 promoters, thus modulating the odontogenic differentiation of DPSCs and dentin formation.

Abstract Background PD-L1 staining using long-stored paraffin sections may not be consistent with the true PD-L1 expression of patients. Therefore, it is necessary to explore the expression of PD-L1(SP142) in paraffin sections of invasive breast cancer with different storage times and the optimal storage temperature for unstained paraffin sections. Methods The study included 71 cases of PD-L1(SP142) positive breast cancer. The unstained paraffin sections were stored at room temperature conditions (20–25 °C), 4 °C, -20 °C and − 80 °C, respectively. PD-L1 staining was performed at 1, 2, 3, 4, 8, 12 and 24 weeks of storage. PD-L1 expression was assessed with a continuity score. Results The PD-L1 antigen was gradually lost as the storage time of paraffin sections increased. The PD-L1 positivity rate was 97.18% at 1 week for the sections stored at room temperature, and decreased from 83.10 to 71.83% for the sections stored for 2 weeks to 4 weeks, and 61.97%, 54.93%, and 32.93% for 8, 12, and 24 weeks, respectively. When stored at low temperatures of 4 °C, -20 °C and − 80 °C, the positivity rate decreases with the same trend but more slowly compared to room temperature. The mean IC score of PD-L1 also showed a gradual decrease in all cases. In the consistency analysis, PD-L1 expression in slices stored at room temperature for 2 weeks was consistent with PD-L1 expression in fresh slices (ICC ≥ 0.9 for all slices), and PD-L1 expression in slices stored at 4 °C or -20 °C for 4 weeks was consistent with PD-L1 expression in fresh slices (ICC ≥ 0.9 for all slices). When stored under refrigeration at -80 °C, PD-L1 expression in slices stored for 3 weeks was consistent with that in fresh slices (ICC ≥ 0.9). Conclusions To our knowledge, this is the first article on the effect of preservation time and preservation temperature of paraffin sections on PD-L1 expression in breast cancer. Long-term storage of paraffin sections of unstained invasive breast cancer can lead to antigen loss of PD-L1 (SP142). Refrigerated storage of paraffin sections can delay antigen loss, with best results at 4 °C or -20 °C, and a storage time of no more than 4 weeks is recommended.

Abstract Two facts about cortex are widely accepted: neuronal responses show large spiking variability with near Poisson statistics and cortical circuits feature abundant recurrent connections between neurons. How these spiking and circuit properties combine to support sensory representation and information processing is not well understood. We build a theoretical framework showing that these two ubiquitous features of cortex combine to produce optimal sampling-based Bayesian inference. Recurrent connections store an internal model of the external world, and Poissonian variability of spike responses drives flexible sampling from the posterior stimulus distributions obtained by combining feedforward and recurrent neuronal inputs. We illustrate how this framework for sampling-based inference can be used by cortex to represent latent multivariate stimuli organized either hierarchically or in parallel. A neural signature of such network sampling are internally generated differential correlations whose amplitude is determined by the prior stored in the circuit, which provides an experimentally testable prediction for our framework.

Abstract Background Image-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensure that patients with early-stage LUAD receive appropriate treatments. Methods We integrated 158 early-stage LUAD cases from 2 independent cohorts, including 30 matched resected specimens with complete radiological and pathological information, and 128 retrospective pathological pair-samples with partial follow-up data. This integration allowed us to conduct a correlation analysis between clinical phenotype and transcriptome landscape. Immunohistochemistry was performed using tissue microarrays to examine the expression of phospholipid phosphatase 2 (PLPP2) and lipid-raft markers. Lipidomics analysis was used to determine the changes of lipid components in PLPP2-overexpressed cells. To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MβCD, respectively. Results Bioinformatics analysis indicated that the co-occurrence of lipid raft formation and rapid cell proliferation might exhibit synergistic effects in driving oncogenesis from lung preneoplasia to adenocarcinoma. The enhanced activation of the cell cycle promoted the transition from non-invasive to invasive status in early-stage LUAD, which was related to an increase in lipid rafts within LUAD cells. PLPP2 participated in lipid raft formation by altering the component contents of lipid rafts, such as esters, sphingomyelin, and sphingosine. Furthermore, elevated PLPP2 levels were identified as an independent prognostic risk factor for LUAD patients. Further results from in vivo and in vitro experiments confirmed that PLPP2 could induce excessive cell proliferation by enhancing lipid raft formation in LUAD cells. Conclusions Our study has revealed the characteristics of gene expression profiles in early-stage LUAD patients with the different radiological and pathological subtypes, as well as deciphered transcriptomic evolution trajectory from preneoplasia to invasive LUAD. Furthermore, it suggests that PLPP2-mediated lipid raft synthesis may be a significant biological event in the initiation of early-stage LUAD, offering a potential target for more precise diagnosis and therapy in clinical settings.

Abstract Preventing tau aggregation is a potential therapeutic strategy in Alzheimer’s disease and other tauopathies. Recently, liquid–liquid phase separation has been found to facilitate the formation of pathogenic tau conformations and fibrillar aggregates, although many aspects of the conformational transitions of tau during the phase transition process remain unknown. Here, we demonstrate that the tau aggregation inhibitor methylene blue promotes tau liquid–liquid phase separation and accelerates the liquid-to-gel transition of tau droplets independent of the redox activity of methylene blue. We further show that methylene blue inhibits the conversion of tau droplets into fibrils and reduces the cytotoxicity of tau aggregates. Although gelation slows down the mobility of tau and tubulin, it does not impair microtubule assembly within tau droplets. These findings suggest that methylene blue inhibits tau amyloid fibrillization and accelerates tau droplet gelation via distinct mechanisms, thus providing insights into the activity of tau aggregation inhibitors in the context of phase transition.

Nest-site selection plays a crucial role in reproductive success and survival of birds, particularly for territorial birds. Therefore, it is important to understand how birds identify and select their nesting sites. The Amur Paradise Flycatcher ( Terpsiphone incei ) is a medium-sized species of the Monarchidae family with dichromatism in males. To investigate the differences in nest-site utilization strategies between different male morphs and identify the nest-site variables that influence the nest success of the species, we conducted a study on nest-site selection and nest success during the breeding seasons of 2020 to 2022 in Yangxian County, Shaanxi Province, China. During our study, we recorded a total of 98 nests and found that the Amur Paradise Flycatcher preferred nesting in forests with lower illumination, specifically on cedrela trees, and exclusively near residential areas. Interestingly, we did not find any significant difference both in nest-site selection and nesting success between the two male morphs. The overall nesting success was 51.06% (n = 94), with nest predation being the primary cause of nest failure. Our principal component analysis identified several significant factors affecting nest-site selection, including nest tree factors (14.168%), interference factors (13.145%), nest concealment factors (10.87%), terrain factors (10.262%), altitude factors (10.046%), and stability factors (8.438%). Furthermore, the results of binary logistic regression analysis indicated that successful breeding nests were located closer to the forest edge, had a sunnier aspect, and a smaller slope compared to failed nests. Similarly, the multiple linear regression analysis showed that slope, aspect, and nest tree species had significant effects on breeding success. Our findings suggest that the Amur Paradise Flycatcher seeks a balance between nest concealment and a view of the surroundings. The lack of a significant difference in reproductive outcomes between the two male morphs could potentially be attributed to the greater experience of white morph individuals, which may help mitigate the higher risk with their more attractive plumage for predators. Understanding the factors affecting nest-site selection and nest success is crucial for conservation efforts aimed at protecting this fascinating species and ensuring its long-term survival.

In digital cameras, we find a major limitation: the image and video form inherited from a film camera obstructs it from capturing the rapidly changing photonic world. Here, we present vform, a bit sequence array where each bit represents whether the accumulation of photons has reached a threshold, to record and reconstruct the scene radiance at any moment. By employing only consumer-level complementary metal–oxide semiconductor (CMOS) sensors and integrated circuits, we have developed a spike camera that is 1000× faster than conventional cameras. By treating vform as spike trains in biological vision, we have further developed a spiking neural network (SNN)-based machine vision system that combines the speed of the machine and the mechanism of biological vision, achieving high-speed object detection and tracking 1000× faster than human vision. We demonstrate the utility of the spike camera and the super vision system in an assistant referee and target pointing system. Our study is expected to fundamentally revolutionize the image and video concepts and related industries, including photography, movies, and visual media, and to unseal a new SNN-enabled speed-free machine vision era.

Elucidating the intricate neural mechanisms underlying brain functions requires integrative brain dynamics modeling. To facilitate this process, it is crucial to develop a general-purpose programming framework that allows users to freely define neural models across multiple scales, efficiently simulate, train, and analyze model dynamics, and conveniently incorporate new modeling approaches. In response to this need, we present BrainPy. BrainPy leverages the advanced just-in-time (JIT) compilation capabilities of JAX and XLA to provide a powerful infrastructure tailored for brain dynamics programming. It offers an integrated platform for building, simulating, training, and analyzing brain dynamics models. Models defined in BrainPy can be JIT compiled into binary instructions for various devices, including Central Processing Unit, Graphics Processing Unit, and Tensor Processing Unit, which ensures high-running performance comparable to native C or CUDA. Additionally, BrainPy features an extensible architecture that allows for easy expansion of new infrastructure, utilities, and machine-learning approaches. This flexibility enables researchers to incorporate cutting-edge techniques and adapt the framework to their specific needs.

Abies ernestii var. salouenensis (Bordères & Gaussen) W. C. Cheng & L. K. Fu is endemic to southwest China, including the southeastern Tibetan Plateau and the northwestern Yunnan Province. The taxonomic relationships between A. ernestii var. salouenensis and two other closely related fir species (A. chensiensis Tiegh. and A. ernestii Rehd.) still need to be determined. Here, we report for the first time the whole chloroplast genome of A. ernestii var. salouenensis. Its genome is 121,759 bp long and is characterized by a circular structure with 68 peptide-encoding genes, 16 tRNAs, six ORFs, and four rRNAs. We also identified 70 microsatellite repeat sequences and 14 tandem repeat sequences in the chloroplast genome of A. ernestii var. salouenensis. Comparative genome analysis indicated considerable variation in ycf1 and ycf2. Phylogenetic analysis supported the monophyly of A. ernestii var. salouenensis, A. chensiensis Tiegh., and A. ernestii Rehd. The relationships among them should be surveyed using more samples at the species level. This study will facilitate taxonomic studies and the development of suitable chloroplast markers for fir species.

Microplastic might affect the crop yield, nitrogen (N) use efficiency and reactive N losses from agricultural soil systems. However, evaluation of these effects in infertile soil planted with different rice cultivars is lacking. We conducted a soil column experiment to determine the influence of a typical microplastic polyethylene (PE) input into an infertile soil with 270 kg N ha−1 and planted with two rice cultivars, i.e., a common rice Nangeng 5055 (NG) and a hybrid rice Jiafengyou 6 (JFY). The results showed that JFY produced a significantly (p < 0.05) greater grain yield than NG (61.6–66.2 vs. 48.2–52.5 g pot−1) but was not influenced by PE. Overall, PE hardly changed the N use efficiency of NG and JFY. Unexpectedly, PE significantly (p < 0.05) increased the total amino acid content of NG. Compared with JFY, NG volatilized significantly (p < 0.05) more ammonia (NH3) (0.84–0.92 vs. 0.64–0.67 g N pot−1) but emitted equal nitrous oxide (N2O). PE exerted no effect on either NH3 volatilization or the N2O emission flux pattern and cumulative losses of the rice growth cycle, whether with NG or JFY. Some properties of tested soils changed after planting with different rice cultivars and incorporating with microplastic. In conclusion, the rice production, N use efficiency, NH3 volatilization and N2O emission from the N-fertilized infertile soil were pronouncedly influenced by the rice cultivar, but not the PE. However, PE influenced the grain quality of common rice and some properties of tested soils with both rice cultivars.

Mesenchymal stem cells (MSCs) have been recognized as a cell therapy with the potential to promote skin healing. MSCs, with their multipotent differentiation ability, can generate various cells related to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. In addition, MSCs promote neovascularization, cellular regeneration, and tissue healing through mechanisms including paracrine and autocrine signaling. Due to these characteristics, MSCs have been extensively studied in the context of burn healing and chronic wound repair. Furthermore, during the investigation of MSCs, their unique roles in skin aging and scarless healing have also been discovered. In this review, we summarize the mechanisms by which MSCs promote wound healing and discuss the recent findings from preclinical and clinical studies. We also explore strategies to enhance the therapeutic effects of MSCs. Moreover, we discuss the emerging trend of combining MSCs with tissue engineering techniques, leveraging the advantages of MSCs and tissue engineering materials, such as biodegradable scaffolds and hydrogels, to enhance the skin repair capacity of MSCs. Additionally, we highlight the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies as a future direction in stem cell-based treatments, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.

BackgroundInvasive micropapillary carcinoma (IMPC) of the breast is a rare subtype of breast cancer with high incidence of aggressive clinical behavior, lymph node metastasis (LNM) and poor prognosis. In the present study, using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed the clinicopathological characteristics and prognostic factors of IMPC with LNM, and constructed a prognostic nomogram.MethodsWe retrospectively analyzed data for 487 breast IMPC patients with LNM in the SEER database from January 2010 to December 2015, and randomly divided these patients into a training cohort (70%) and an internal validation cohort (30%) for the construction and internal validation of the nomogram, respectively. In addition, 248 patients diagnosed with IMPC and LNM at the Fourth Hospital of Hebei Medical University from January 2010 to December 2019 were collected as an external validation cohort. Lasso regression, along with Cox regression, was used to screen risk factors. Further more, the discrimination, calibration, and clinical utility of the nomogram were assessed based on the consistency index (C-index), time-dependent receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA).ResultsIn summary, we identified six variables including molecular subtype of breast cancer, first malignant primary indicator, tumor grade, AJCC stage, radiotherapy and chemotherapy were independent prognostic factors in predicting the prognosis of IMPC patients with LNM (P < 0.05). Based on these factors, a nomogram was constructed for predicting 3- and 5-year overall survival (OS) of patients. The nomogram achieved a C-index of 0.789 (95%CI: 0.759-0.819) in the training cohort, 0.775 (95%CI: 0.731-0.819) in the internal validation cohort, and 0.788 (95%CI: 0.756-0.820) in the external validation cohort. According to the calculated patient risk score, the patients were divided into a high-risk group and a low-risk group, which showed a significant difference in the survival prognosis of the two groups (P

TCP transcription factors are a type of plant-specific transcription factors, which have been implicated in multiple aspects of plant biological processes. To study the role of potato TCP transcription factors in response to low nitrogen fertilizer stress, here, four transcriptome libraries from potato roots and leaves under the conditions of low nitrogen fertilizer (0.05 mmol·L-1) and sufficient nitrogen fertilizer (7.5 mmol·L-1) were constructed for transcriptome sequencing, respectively. Meanwhile, the differentially expressed TCP transcription factor were analyzed. The results were as follows: (1) A total of 24 TCP transcription factors were identified in the four transcriptome libraries, and mainly distributed on the second, third and sixth chromosomes. (2) The analysis of domains showed that all of 24 transcription factors contained basic-Helix-Loop-Helix domain. (3) The phylogenetic analysis showed that the TCP proteins of potato and Arabidopsis thaliana were closely related, and clustered into ten subgroups. (4) Transcriptome sequencing results showed that the expression levels of most potato TCP transcription factors were suppressed by low nitrogen fertilizer stress. Among them, three TCP transcription factors were significantly differentially expressed in roots, while five TCP transcription factors were specifically expressed in leaves. (5) According to the GO functional analysis and the relationship between the potato and the A. thaliana TCP transcription factors, it is predicted that these TCP transcription factors were involved in response of potato to low nitrogen fertilizer stress. The research provides a foundation for further study on the molecular role of transcription factors in response to low nitrogen fertilizer stress in potato and other crops.

The integration of multiple stimuli-responsiveness in artificial materials usually causes mutual interference, which makes artificial materials work improperly. Here, the authors design composite gels with organic‒inorganic semi-interpenetrating network structures, which are orthogonally responsive to light and magnetic fields.

Abstract Neoadjuvant therapy (NAT) treats early‐stage breast cancers, especially triple‐negative breast cancers (TNBCs). NAT improves pathological complete response (pCR) rates for different breast cancer patients. Recently, immune checkpoint inhibitors that target programmed death 1 (PD‐1) or programmed death ligand 1 (PD‐L1) in combination with NAT have shown antitumor activity in patients with early breast cancer. However, the tumor immune microenvironment (TME) in different subtypes of breast cancers, like TNBC, hormone receptor‐positive (HR+), and human epidermal growth factor receptor 2 amplified (HER2+) and its changes by NAT remain to be fully characterized. We analyzed pre‐NAT tumor biopsies from TNBC (n = 27), HR+ (n = 24), and HER2+ (n = 30) breast cancer patients who received NAT, followed by surgery. The different immune makers (PD‐1, PD‐L1, CD3, and CD8) of tumor‐infiltrating lymphocytes (TILs) were identified with immunofluorescence‐based microenvironment analysis. TILs within cancer parenchyma (iTILs) and in cancer stroma (sTILs) were counted separately. We found that PD‐L1+ cells in tumor and stroma were significantly higher in TNBC patients than in others. PD‐L1+ sTILs were significantly higher in pCR than in non‐pCR patients of all the subtypes. The infiltration scores of B‐cell memory, T‐cell CD4+ memory activated, T‐cell follicular helper, and Macrophage M0 and M1 were relatively higher in TNBC patients, indicating immunoreactive TME in TNBC. Analysis of TCGA‐BRCA RNA‐seq indicated that PD‐L1 was highly expressed in TNBC patients compared with HR+ and HER2+ patients. Higher PD‐L1 expression in TNBC patients was associated with significantly longer overall survival (OS). Our results demonstrated that PD‐L1 expression level of iTILs and sTILs is highest in TNBC among breast cancers. TNBC patients had significantly different immunoreactive TME compared with HR+ and HER2+ patients, suggesting potentially favorable outcomes for immunotherapy in these patients. Also, PD‐L1+ could be a powerful predictor of pCR in TNBC patients after NAT.

Infertility has become a serious disease since it affects 10%–15% of couples worldwide, and male infertility contributes to about 50% of the cases. Notably, a significant decrease occurs in the newborn population by 7.82 million in 2020 compared to 2016 in China. As such, it is essential to explore the effective methods of obtaining functional male gametes for restoring male fertility. Stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), spermatogonial stem cells (SSCs), and mesenchymal stem cells (MSCs), possess the abilities of both self-renewal and differentiation into germ cells. Significantly, much progress has recently been achieved in the generation of male germ cells in vitro from various kinds of stem cells under the specified conditions, e.g., the coculturing with Sertoli cells, three-dimensional culture system, the addition of growth factors and cytokines, and/or the overexpression of germ cell-related genes. In this review, we address the current advance in the derivation of male germ cells in vitro from stem cells based on the studies of the peers and us, and we highlight the perspectives and potential application of stem cell-derived male gametes in reproductive medicine.

Cavitation is a challenging flow phenomenon that can adversely affect the hydraulic performance of centrifugal pumps. In this study, numerical investigations were carried out incorporating the Zwart cavitation model derived from Rayleigh–Plesset equation with the Navier–Stokes equations to study a damaged turbofan pump. Pressure fluctuation was analyzed with fast Fourier transform (FFT) in both non-cavitation and cavitation flow fields. The entropy production theory was used to further analyze the positions of vortex cores and energy-loss behaviors inside the pump. The results demonstrate that the numerically predicted positions of vortex cores in high-pressure regions agree well with the erosion positions determined under real working conditions. Herein, through combined analysis of the pressure contours and the vortex-core locations, we demonstrate that the erosion failure of the surface is caused by fatigue failure due to the collapse of cavities at vortex cores. The percentages of different kinds of entropy production rates under different mass flow rates in the whole calculation domain were calculated, and it was found that the impeller suffered the most energy loss. The results of the entropy production analysis can provide guidance for subsequent optimization of turbofan pumps.

Abstract Background The cultivated Camellia sasanqua forms a divergent double flower pattern, and the stamen petaloid is a vital factor in the phenomenon. However, the regulation mechanism remains largely unclear. Results Here, a comprehensive comparative transcriptome analysis of the wild-type, “semi-double”, “peony double”, and “rose double” was performed. The cluster analysis of global gene expression level showed petal and stamen difficulty separable in double flower. The crucial pathway and genes related to double flower patterns regulation were identified by pairwise comparisons and weighted gene coexpression network (WGCNA). Divergent genes expression, such as AUX1 and AHP, are involved in plant hormone signaling and photosynthesis, and secondary metabolites play an important role. Notably, the diversity of a petal-specific model exhibits a similar molecular signature to the stamen, containing extensin protein and PSBO1, supporting the stamen petaloid point. Moreover, the expansion of class A gene activity influenced the double flower formation, showing that the key function of gene expression was probably demolished. Conclusions Overall, this work confirmed the ABCE model and provided new insights for elucidating the molecular signature of double formation.

For all organs at all Cymbidium faberi stages, ACT, UBQ3 and GAPDH can be selected as reference genes. For organs of the vegetative stage, UBQ2 and UBQ3 can be chosen for analysis of normalized gene expression. For the bud stage, ACT and UBQ3 can be used for analysis of gene expression. For the full blossom stage, ACT, UBQ3 and UBQ2 can be introduced into relative gene expression analysis. For vegetative organs, UBQ2 and ACT can be used as reference genes. For reproductive organs, ACT, UBQ3 and UBQ2 can be used as a reference for data processing. CfAG1 gene expression is more consistent when UBQ3, GAPDH and ACT are used as reference genes.

Spermatogenesis is regulated by genetic and epigenetic factors. However, the genes and signaling pathways mediating human spermatogenesis remain largely unknown. Here, we have for the first time explored the expression, function, and mechanism of glutathione peroxidase 3 (GPx3) in controlling the proliferation and apoptosis of human spermatogonial stem cells (SSCs). We found that GPx3 was expressed in human SSCs. Notably, we revealed that GPx3 knockdown resulted in the decrease in the proliferation, DNA synthesis, and cyclin B1 level in human SSC lines, which possessed the phenotypic features of human primary SSCs. Flow cytometry and TUNEL assays showed that GPx3 silencing led to enhancement of early apoptosis of human SSC line. RNA sequencing was utilized to identify CXCL10 as a target of GPx3 in human SSCs, and notably, both double immunostaining and co-immunoprecipitation (co-IP) demonstrated that there was an association between GPx3 and CXCL10 in these cells. CXCL10-shRNA resulted in the reduction in the proliferation and DNA synthesis of human SSC line and an increase in apoptosis of these cells. Taken together, these results implicate that GPx3 regulates the proliferation, DNA synthesis, and early apoptosis of human SSC line via mediating CXCL10 and cyclin B1. This study, thus, offers a novel insight into the molecular mechanism regulating the fate determinations of human SSCs and human spermatogenesis.

Random lasers (RLs), which possess peculiar advantages (e.g., emission and coherence tunable) over traditional lasers with optical resonators, have witnessed rapid development in the past decades. However, it is still a challenge to tune the lasing peak of an RL over a wide range. Here, a temperature-dependent Förster resonance energy transfer (FRET) RL is demonstrated in pyrromethene 597 (PM597, “donor”) and Nile blue (NB, “acceptor”) doped chiral liquid crystals. By changing the temperature that drives the liquid crystal bandgap shift, our RL device exhibits a lasing output change from 560 nm (yellow) to 700 nm (red). While the intrinsic FRET efficiency between PM597 and NB is relatively low, the red lasing is weak. By introducing gold nanorods (GNRs) into these RL devices and utilizing GNRs’ localized surface plasmon resonance (LSPR) effect, the efficiency of FRET transfer is increased by 68.9%, thereby reducing the threshold of the RL devices. By tuning the longitudinal LSPR to match the emission wavelength of NB, the best 200-fold lasing intensity enhancement is recorded. Our findings open a pathway toward realizing LSPR-enhanced FRET tunable RLs and broaden the range of their possible exploration in photonics research and technologies.

To investigate the responses of crop production and soil profile nutrient status to biochar (BC) application, we conducted a soil column experiment considering two BC addition rates (0.5 and 1.5 wt% of the weight of 0–20 cm topsoil) combined with two nitrogen (N) input levels (low N: 144 kg ha−1, LN; high N: 240 kg ha−1, HN). The results showed that BC application increased the soil pH. The soil pH of the 0–10 cm profile under LN and the 20–40 cm profile under HN were both significantly increased by 0.1–0.2 units after BC addition. Under LN, BC addition significantly increased NH4+-N (17.8–46.9%), total N (15.4–38.4%), and soil organic carbon (19.9–24.0%) in the 0–10 cm profile, but decreased NH4+-N in the 20–30 cm soil profile and NO3−-N in the 10–30 cm profile by 13.8–28.5% and 13.0–34.9%, respectively. BC had an increasing effect on the available phosphorus, the contents of which in the 10–20 and 30–40 cm soil profiles under LN and 20–30 cm profile under HN were significantly elevated by 14.1%, 24.0%, and 23.27%, respectively. However, BC exerted no effect on the available potassium in the soil profile. BC had a strong improving effect (15.3%) on the wheat yield, especially the N144 + BC0.5% treatment, which could be compared to the HN treatment, but there was no yield-increasing effect when high N fertilizer was supplied. In summary, BC improved the fertility of agriculture soil (0–20 cm) with wheat. In particular, low N inputs together with an appropriate rate of BC (0.5 wt%) could not only achieve the low inputs but also the high outputs in wheat production. In future study, we will compare the effects of multiple doses of N and BC on soil fertility and crop production.

Abstract Background Mosquitoes locate a human host by integrating various sensory cues including odor, thermo, and vision. However, their innate light preference and its genetic basis that may predict the spatial distribution of mosquitoes, a prerequisite to encounter a potential host and initiate host-seeking behaviors, remains elusive. Results Here, we first studied mosquito visual features and surprisingly uncovered that both diurnal (Aedes aegypti and Aedes albopictus) and nocturnal (Culex quinquefasciatus) mosquitoes significantly avoided stronger light when given choices. With consistent results from multiple assays, we found that such negative phototaxis maintained throughout development to adult stages. Notably, female mosquitoes significantly preferred to bite hosts in a shaded versus illuminated area. Furthermore, silencing Opsin1, a G protein-coupled receptor that is most enriched in compound eyes, abolished light-evoked avoidance behavior of Aedes albopictus and attenuated photonegative behavior in Aedes aegypti. Finally, we found that field-collected Aedes albopictus also prefers darker area in an Opsin1-dependent manner. Conclusions This study reveals that mosquitoes consistently prefer darker environment and identifies the first example of a visual molecule that modulates mosquito photobehavior.

Dongting Lake Plain is a historic foundation for China’s commodity grain production. We used Landsat images to interpret the rice planting pattern from 1990 to 2020 based on the vegetation index curve and crop time window differences. The research aims included the spatiotemporal change in the rice planting area and the multiple cropping index, the transformation properties between single-crop and double-crop, and influence factors of rice cultivation. The findings indicated that the rice planting area has increased by 23.64% over the past 30 years. However, the multiple cropping index decreased by 17.39%. The area of single-crop rice increased by 2.6 times, while the area of double-crop rice decreased by 23.19%, which indicated that the planting intensity of rice has decreased. The area where rice has been steadily planted for 30 years is approximately 5600 km2, accounting for 87% of all rice planting land in this study area. The transformation from double-crop rice to single-crop rice was the most obvious characteristic of internal changes. The marginal benefits of current agricultural policies have decreased. This research may provide a theoretical basis for the refined management of rice and improve agricultural policies. More clouds in the remote sensing image limited the time resolution. Future research may further explore the comprehensive influencing factors.

Abstract The present study aimed to distinguish different hypertriglyceridemic waist phenotypes and relevant risks of developing fatty liver and abnormal glycometabolic profiles in overweight/obese adults. A total of 1221 Chinese adults with mean (standard deviation [SD]) age of 37 (9) years, 37.3% males and 62.7% females, body mass index (BMI) of 29.0 (4.0) kg/m2, triglyceride (TG) 2.04 (1.45) mmol/L, and waist circumference (WC) 95.8 (10.7) cm were included and classified into four phenotypes: normal TG & normal WC (N-N); normal TG & high WC (N-WC); high TG & normal WC (TG-N); high TG & high WC (TG-WC). Participants in TG-WC group had the highest BMI, WC, blood pressure (BP), insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL), and fatty liver. Participants within N-WC group had a significantly higher risk of fatty liver (adjusted OR 3.50 [95% CI 2.05–5.97]), as well as TG-N (adjusted OR 2.59 [95% CI 1.61–4.16]) and TG-WC (adjusted OR 4.12 [95% CI 2.28–7.46]). The risk of elevated HOMA-IR was significantly higher in TG-N (adjusted OR 2.16 [95% CI 1.33–3.50]) and TG-WC (adjusted OR 2.04 [95% CI 1.22–3.40]). The risk of elevated HbA1c was significantly higher in the TG-WC (adjusted OR 2.79 [95% CI 1.47–5.31]). Hypertriglyceridemic waist phenotype can be a potential and cost-effective method to identify individuals with a high risk of fatty liver and glycometabolic disorders.

Selection of reference genes (RGs) is important for the accurate analysis of real-time quantitative PCR (RT-qPCR) results. This study screened RGs of Cymbidium sinense for more accurate quantification of target genes. The two most stable RGs for all tissues were ACT and EF1α, those for vegetative organs were UBQ3 and ACT, while those for reproductive organs as well as organs in the full flowering stage were EF1α and ACT. The AGAMOUS (CsAG1) expression level was verified using EF1α, ACT, GAPDH, UBQ2 and UBQ3 as RG. The expression profile of CsAG1 was consistent when normalized with EF1α, ACT and UBQ3. The results have practical value for the expression of key genes during the development of C. sinense.

BackgroundThe emergence of HER2 antibody-drug conjugates provides new treatment decisions for breast cancer patients, especially those with HER2-low expression. In order to explore the biological characteristics of breast cancer with HER2-low expression, the HER2-low category in primary breast cancer and residual tumor after neoadjuvant therapy was investigated to reflect the evolution of HER2 expression.MethodsHER2 was assessed according to the latest ASCO/CAP guidelines. The cut-off value for staining of HER2-positive cells was >10%. HER2-negative cases were divided into HER2-low (IHC=1+/2+ and no ISH amplification) and HER2-zero (IHC-0), and the clinicopathological characteristics of the cases were collected.ResultsThis study included 1140 patients with invasive breast cancer who received preoperative neoadjuvant therapy from 2018 to 2021, of which 365 patients achieved pCR and 775 were non-pCR. In the non-pCR cohort, HER2-low cases accounted for 59.61% of primary tumors and 55.36% of residual tumors. Among HER2-negative cases, HR-positive tumors had a higher incidence of low HER2 expression compared with triple-negative tumors (80.27% vs 60.00% in primary tumors and 72.68% vs 50.77% in residual tumors). The inconsistency rate of HER2 expression was 21.42%, mainly manifested as the conversion of HER2-low cases to HER2-zero (10.19%) and the conversion of HER2-zero to HER2-low (6.45%). Among the HER2-negative cases in the primary tumor, the HER2 discordance rate of HR-positive cases was lower than that of triple-negative cases (23.34% VS 36.92%). This difference was mainly caused by the case switching from HER2-low to HER2-zero. Compared with HER2-zero cases, there were statistically significant differences in RCB grade, MP grade and the number of metastatic lymph nodes in HER2-low cases. Patients with low HER2 expression had a lower pathological response rate and a higher number of metastatic lymph nodes.ConclusionHER2-low breast cancer is highly unstable during disease evolution and has certain biological characteristics. HER2-low breast cancer is not only correlated with positive HR, but also has a certain correlation with positive AR. Re-detection of HER2 in breast cancer after neoadjuvant therapy may lead to new treatment opportunities for a certain proportion of patients.

With prominent environmental pollution and depleted resources, how to coordinate economic growth and eco-environmental protection to guide green development represented by green total factor productivity (GTFP) is an urgent issue. This study aims to empirically evaluate the direct effect, indirect effect, spatial spillover effect and non-linear effect of the digital economy on green development using the data of 284 prefecture-level cities in China. The empirical results indicate that: (1) the digital economy significantly improves GTFP, which is still valid after testing for robustness, including introducing instrumental variables, taking the “broadband China” pilot policy as a quasi-natural experiment, changing core explanatory variables and dependent variables, and changing the sample size; (2) the influence of the digital economy on GTFP is characterized by significant heterogeneity among resource dependence, geographical location, financial development level and openness level; (3) the mechanism analysis shows that the digital economy promotes GTFP by green technological innovation, industrial structure upgrading and energy conservation; (4) the spatial econometric models indicate that the digital economy significantly enhances GTFP of neighboring cities; (5) there is a non-linear relationship between the digital economy and GTFP using the threshold model. The findings could provide references for policymakers to promote urban green development.

Persistent infection with human papillomavirus (HPV) types 31 and 33 is an important causative factor for cervical cancer. The E6/E7 genes are key oncogenes involved in the immortalization and transformation of human epithelial cells. Genetic polymorphism may lead to differences in the virus’ carcinogenic potential, the immune reaction of the host, and the potencies of vaccines. Few studies on HPV31/33 E6/E7 genetic polymorphism have been carried out. To study the genetic polymorphism of HPV31 and HPV33 E6/E7 genes in northeast China, these genes (HPV31 E6/E7, n = 151; HPV33 E6/E7, n = 136) were sequenced and compared to reference sequences (J04353.1, M12732.1) using BioEdit. Phylogenetic trees were constructed by the neighbor-joining method using MegaX. The diversity of the secondary structure was estimated using the PSIPred server. The positively selected sites were analyzed using PAML4.9. The major histocompatibility complex (MHC) class I and MHCII epitopes were predicted using the ProPred-I server and ProPredserver. B-cell epitopes were predicted using the ABCpred server. In the 151 HPV31E6 sequences, 25 (25/450) single-nucleotide mutations were found, 14 of which were synonymous mutations and 11 were nonsynonymous. In the 151 HPV31E7 sequences, 8 (8/297) nucleotide mutations were found, 3 of which were synonymous mutations and 5 were nonsynonymous. In the 136 HPV33E6 sequences, 17 (17/450) nucleotide mutations were observed, 7 of which were synonymous mutations and 10 were nonsynonymous. C14T/G (T5I/S) was a triallelic mutation. Finally, in the 136 HPV33E7 sequences, 9 (9/294) nucleotide mutations were observed, 3 of which were synonymous mutations and 6 were nonsynonymous. C134T/A (A45V/E) and C278G/A (T93S/N) were triallelic mutations. Lineage A was the most common lineage in both HPV31 and HPV33. In all of the sequences, we only identified one positively selected site, HPV33 E6 (K93N). Most nonsynonymous mutations were localized at sites belonging to MHC and/or B-cell predicted epitopes. Data obtained in this study should contribute to the development and application of detection probes, targeted drugs, and vaccines.

Self-assembly of colloidal nanoparticles is a promising approach for the fabrication of functional materials. Zeta potential strongly influences the self-assembly processes of nanoparticles. Light-induced zeta potential manipulation provides spatiotemporal resolution. However, current studies on photo-controllable zeta potential are based on ultraviolet (UV) light. In comparison with UV light, visible light is better suited to control the zeta potential of colloidal nanoparticles. In the present study, we applied visible light-responsive ruthenium (Ru) complexes, grafted onto the surface of silica nanoparticles (Ru-SNPs), to control their assembly. The Ru complexes were photoresponsive. Irradiation of Ru-SNPs induced the release of Ru complexes from the nanoparticle surface. The released Ru caused a decrease in the zeta potential of colloidal Ru-SNPs that further changed the assembly behavior and led to the aggregation of Ru-SNPs.

Abstract Background Drought is a major environmental disaster that causes crop yield loss worldwide. Metabolites are involved in various environmental stress responses of plants. However, the genetic control of metabolomes underlying crop environmental stress adaptation remains elusive. Results Here, we perform non-targeted metabolic profiling of leaves for 385 maize natural inbred lines grown under well-watered as well as drought-stressed conditions. A total of 3890 metabolites are identified and 1035 of these are differentially produced between well-watered and drought-stressed conditions, representing effective indicators of maize drought response and tolerance. Genetic dissections reveal the associations between these metabolites and thousands of single-nucleotide polymorphisms (SNPs), which represented 3415 metabolite quantitative trait loci (mQTLs) and 2589 candidate genes. 78.6% of mQTLs (2684/3415) are novel drought-responsive QTLs. The regulatory variants that control the expression of the candidate genes are revealed by expression QTL (eQTL) analysis of the transcriptomes of leaves from 197 maize natural inbred lines. Integrated metabolic and transcriptomic assays identify dozens of environment-specific hub genes and their gene-metabolite regulatory networks. Comprehensive genetic and molecular studies reveal the roles and mechanisms of two hub genes, Bx12 and ZmGLK44, in regulating maize metabolite biosynthesis and drought tolerance. Conclusion Our studies reveal the first population-level metabolomes in crop drought response and uncover the natural variations and genetic control of these metabolomes underlying crop drought adaptation, demonstrating that multi-omics is a powerful strategy to dissect the genetic mechanisms of crop complex traits.

Fluorescence imaging is a noninvasive technique that affords real‐time fast feedback, high sensitivity, and harmless radiation and is thus effective in visualizing the anatomy and function of organs. Recently, second near‐infrared (NIR‐II, 1000–1700 nm) fluorescence imaging emerged as a popular imaging technique for both fundamental research and clinical practice, with strong potential for applications in the field of biomedicine. It affords a high signal‐to‐noise ratio and high spatial and temporal resolutions for the imaging of deep tissue owing to reduced scattering, minimal absorption, and negligible autofluorescence. Herein, the performance and advancement of fluorophores for NIR‐II fluorescence imaging are summarized. Further, the challenges to the NIR‐II fluorophores in terms of emission wavelengths, quantum yields, stability, targeting, and biocompatibility are discussed. Finally, perspective on the current development and the orientation for future studies on NIR‐II imaging, such as dual‐mode imaging, multiplexed imaging, surgical navigation, integrated diagnosis and treatment, and biosensing are discussed.

It is of agronomic importance to apply nitrogen (N), but it has high environmental risks in reclaimed saline soils. Therefore, we should apply N fertilizer at an appropriate rate to increase crop yield but decrease N losses. In this soil column experiment, rice yield, N uptake, and ammonia (NH3) and nitrous oxide (N2O) losses were measured in four treatments with no N application (control) and with N applications of 160, 200, and 240 kg/ha (N160, N200, and N240, respectively). The results show that grain yield, spike number, and thousand-kernel weight increased with increases in N application rate, but there was no significant difference in grain yield between N200 and N240. However, the kernels per spike increased first and then decreased with the increase in N application, of which N200 was recorded to have the highest kernels per spike value, which was 16.8 and 9.8% higher than those of N160 and N240, respectively. Total NH3 volatilization of the rice season increased with increasing N input, especially during the first and second supplementary fertilization stages. The NH4+-N concentration of overlying water was relatively lower under the N200 treatment in these two stages, and the yield-scaled NH3 volatilization and the emission factor were the lowest in N200, which were 26.2–27.8% and 4.0–21.0% lower than those of N160 and N240, respectively. Among the three N-applied treatments, N2O losses and the emission factor as well as the yield-scaled N2O emissions were the lowest under the N200 treatment, which had 34.7% and 78.9% lower N2O emissions and 57.8% and 83.5% lower emission factors than those of the N160 and N240 treatments, respectively. Moreover, the gene copies of AOA and AOB amoA, nirS, and nirK in cultivated layer soils all reached the minimum under the N200 treatment. According to the comprehensive effects of N fertilizer on rice grain yield and NH3 and N2O losses, we recommend applying 200 kg/ha to reclaimed saline soil to ensure crop yield and reduce N losses.

BackgroundThe reported rate of cardiovascular adverse events (CAE) caused by immune checkpoint inhibitors (ICI) is low but potentially fatal. Assess the risk of CAE in cancer patients and compare the incidence of CAE between Chinese developed ICIs and imported ICIs.MethodsA retrospective analysis was performed on cancer patients treated with ICI for at least four cycles in the Second Affiliated Hospital of Dalian Medical University from January 2018 to March 2022. Baseline characteristics, physiological and biochemical values, electrocardiographic and echocardiographic findings were compared between patients with and without CAE.ResultsAmong 495 patients treated with ICIs, CAEs occurred in 64 patients (12.93%). The median time to the event was 105 days (61–202). The patients with low neutrophil-to-lymphocyte ratio (L-NLR) were significantly associated with the risk of developing CAE (hazard ratio HR 3.64, 95% confidence ratio CI 1.86–7.15, P = 0.000). Patients with higher comorbidity burden significantly increased the risk of developing CAE (HR 1.30, 95% CI 1.05–1.61, P = 0.014). Those who received a combination of ICI and vascular endothelial growth factor receptor (VEGFR) inhibitors (HR 2.57, 95% CI 1.37–4.84, P = 0.003) or thoracic radiation therapy (HR 32.93, 95% CI 8.81–123.14, P = 0.000) were at a significantly increased risk of developing CAE. Compared to baseline values, creatine kinase is -oenzymes (CK-MB) (95% CI -9.73 to -2.20, P = 0.003) and cardiac troponin I (cTnI) (95% CI -1.06 to -0.06, P = 0.028) were elevated, and the QTc interval prolonged (95% CI -27.07 to -6.49, P = 0.002). Using nivolumab as a control, there was no difference in CAE risk among the eight ICIs investigated. However, the results of the propensity matching showed that programmed death-ligand 1 (PD-L1) inhibitors had lower CAE occurrence compared with programmed cell death protein 1 (PD-1) inhibitors (adjusted HR = 0.38, P = 0.045).ConclusionPatients who received concurrent VEGFR inhibitors and ICIs had a history of thoracic radiation therapy, L-NLR, and higher comorbidity burden had an increased risk of CAEs. Elevated cTnI, CK-MB, and QTc, can be used to monitor CAEs. There was no significant difference in CAE risks between Chinese domestic and imported ICIs. PD-L1 inhibitors had lower CAE occurrence than PD-1 inhibitors.

Most osteoporosis (OP) fracture accidents in men are due not only to a low BMD but also because of unhealthy muscle support. However, there has been a limited number of reports about how muscle metabolism is disturbed by OP in males. In this work, a pathway analysis based on metabolomic research was carried out to fill this gap. A classical orchiectomy procedure was adapted to create an OP animal model. A micro-CT and pathological section were applied for a bone and muscle phenotype assessment and a pathology analysis. UPLC-Q-TOF/MS and UPLC-QQQ-MS/MS were applied to measure metabolites in skeletal muscle samples among groups. In total, 31 significantly differential metabolites were detected by comparing healthy models and OP animals, and 7 representative metabolites among the 31 significantly differential metabolites were identified and validated experimentally by UPLC-QQQ-MS/MS (xanthine, L-phenylalanine, choline, hypoxanthine, L-tryptophan, succinic acid, and L-tyrosine). An ingenuity pathway analysis (IPA) analysis revealed significantly enriched pathways involved in inflammation, oxidative stress, and necrosis. To our best knowledge, this is the first study to investigate early muscle disorder processes in Cases of OP at a metabolic level, facilitating early intervention and protection from OP fractures for aged men.

Abstract Background Postmenopausal osteoporosis (PMO) that results from estrogen withdrawal is the most common primary osteoporosis among older women. However, little is known about the mechanism of PMO, and effective treatment of PMO is limited. Methods We used real-time polymerase chain reaction (qPCR), Western blotting, and RNA pull down to investigate the relationship between miR-186 and MOB Kinase Activator 1A (Mob1). Also, we investigated the effect of exosome in osteogenesis using alkaline phosphatase (ALP) staining. And hematoxylin eosin (HE) staining was used to verify the osteogenesis in PMO model. Results Exosomal miR-186 plays an important role in bone formation. The results of miRNA-seq and q-PCR showed that miR-186 was upregulated in a PMO + Exo treatment group. Results of RNA-pull down and luciferase reporter assays verified interactions between miR-186 and Mob1. We also verified the Hippo signaling pathway plays an important role in osteogenesis. Conclusions We concluded that exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) can transfer miR-186 to promote osteogenesis in ovariectomy (OVX) rats through the Hippo signaling pathway.

Summary: We report a combined experimental and theoretical study on intriguing magnetic properties of quasiferroelectric orthochromates. Large single crystals of the family of RECrO3 (RE = Y, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) compounds were successfully grown. Neutron Laue study indicates a good quality of the obtained single crystals. Applied magnetic field and temperature dependent magnetization measurements reveal their intrinsic magnetic properties, especially the antiferromagnetic (AFM) transition temperatures. Density functional theory studies of the electronic structures were carried out using the Perdew-Burke-Ernzerhof functional plus Hubbard U method. Crystallographic information and magnetism were theoretically optimized systematically. When RE3+ cations vary from Y3+ and Eu3+ to Lu3+ ions, the calculated t-e orbital hybridization degree and Néel temperature behave similarly to the experimentally determined AFM transition temperature with variation in cationic radius. We found that the t-e hybridization is anisotropic, causing a magnetic anisotropy of Cr3+ sublattices. This was evaluated with the nearest-neighbor J1-J2 model. Our research provides a picture of the electronic structures during the t-e hybridization process while changing RE ions and sheds light on the nature of the weak ferromagnetism coexisting with predominated antiferromagnetism. The available large RECrO3 single crystals build a platform for further studies of orthochromates.

Summary: During the early development of the mammalian visual system, the distribution of neuronal preferred orientations in the primary visual cortex (V1) gradually shifts to match major orientation features of the environment, achieving its optimal representation. By combining computational modeling and electrophysiological recording, we provide a circuit plasticity mechanism that underlies the developmental emergence of such matched representation in the visual cortical network. Specifically, in a canonical circuit of densely-interconnected pyramidal cells and inhibitory parvalbumin-expressing (PV+) fast-spiking interneurons in V1 layer 2/3, our model successfully simulates the experimental observations and further reveals that the nonuniform inhibition plays a key role in shaping the network representation through spike timing-dependent plasticity. The experimental results suggest that PV + interneurons in V1 are capable of providing nonuniform inhibition shortly after vision onset. Our study elucidates a circuit mechanism for acquisition of prior knowledge of environment for optimal inference in sensory neural systems

Abstract Self‐fluorescent polymers with different fluorescent chromophores have attracted considerable attention in the field of fluorescence bioimaging due to their tunable topologies and compositions, which render high fluorescence intensity and multicolor photoluminescence. In this Review, recent advances into the construction of self‐fluorescent polymers via the integration of conventional fluorescent chromophores, such as fluorescent dyes and conjugated polymers, and nonconventional heteroatom‐containing chromophores are summarized. In addition, the classification and bonding modes of fluorescent chromophores in polymer backbones, fluorescence mechanisms, and multicolor photoluminescence are discussed. Finally, the promising applications of self‐fluorescent polymers for fluorescence bioimaging are highlighted.

Abstract The development of photo-controlled adhesives can overcome the problems associated with daily lives and industrial applications. Adhesion is a multidiscipline field of engineering, physics, and chemistry. The solid-to-liquid transformation of light-controlled adhesives can be used for direct bonding onto diverse surfaces. Here, a photoresponsive azobenzene compound is developed for photo-controlled adhesion. The azobenzene compound 4, 4'-hexyl diacrylate-3-methylazobenzene (M1) exhibits photoinduced solid-to-liquid transition due to trans–cis photoisomerization. The prepolymer coating based on the azobenzene compound M1 is prepared on an adhesive surface. After UV irradiation, the solid coating was quickly transformed into liquid for adhesion. This photo-controlled adhesive has strong adhesion to different surfaces.