Conjoint analysis of physio-biochemical, transcriptomic, and metabolomic reveals the response characteristics of solanum nigrum L. to cadmium stress.

Cadmium (Cd) is a nonessential element in plants and has adverse effects on the growth and development of plants. However, the molecular mechanisms of Cd phytotoxicity, tolerance and accumulation in hyperaccumulators Solanum nigrum L. has not been well understood. Here, physiology, transcriptome, and metabolome analyses were conducted to investigate the influence on the S. nigrum under 0, 25, 50, 75 and 100 µM Cd concentrations for 7 days. Pot experiments demonstrated that compared with the control, Cd treatment significantly inhibited the biomass, promoted the Cd accumulation and translocation, and disturbed the balance of mineral nutrient metabolism in S. nigrum, particularly at 100 µM Cd level. Moreover, the photosynthetic pigments contents were severely decreased, while the content of total protein, proline, malondialdehyde (MDA), H2O2, and antioxidant enzyme activities generally increased first and then slightly declined with increasing Cd concentrations, in both leaves and roots. Furthermore, combined with the previous transcriptomic data, numerous crucial coding-genes related to mineral nutrients and Cd ion transport, and the antioxidant enzymes biosynthesis were identified, and their expression pattern was regulated under different Cd stress. Simultaneously, metabolomic analyses revealed that Cd treatment significantly changed the expression level of many metabolites related to amino acid, lipid, carbohydrate, and nucleotide metabolism. Metabolic pathway analysis also showed that S. nigrum roots activated some differentially expressed metabolites (DEMs) involved in energy metabolism, which may enhance the energy supply for detoxification. Importantly, central common metabolism pathways of DEGs and DEMs, including the "TCA cycle", "glutathione metabolic pathway" and "glyoxylate and dicarboxylate metabolism" were screened using conjoint transcriptomics and metabolomics analysis. Our results provide some novel evidences on the physiological and molecular mechanisms of Cd tolerance in hyperaccumulator S. nigrum plants.

Bioorthogonal Aptamer-ATTEC Conjugates for Degradation of Alpha-Synuclein via Autophagy-Lysosomal Pathway.

Autophagosome-tethering compound (ATTEC) technology has recently been emerging as a novel approach for degrading proteins of interest (POIs). However, it still faces great challenges in how to design target-specific ATTEC molecules. Aptamers are single-stranded DNA or RNA oligonucleotides that can recognize their target proteins with high specificity and affinity. Here, ATTEC is combined with aptamers for POIs degradation. As a proof of concept, pathological protein α-synuclein (α-syn) is chosen as the target and an efficient α-syn degrader is generated. Aptamer as a targeting warhead of α-syn is conjugated with LC3B-binding compound 5,7-dihydroxy-4-phenylcoumarin (DP) via bioorthogonal click reaction. It is demonstrated that the aptamer conjugated with DP is capable of clearing α-syn through LC3 and autophagic degradation. These results indicate that aptamer-based ATTECs are a versatile approach to degrade POIs by taking advantage of the well-defined different aptamers for targeting diverse proteins, which provides a new way for the design of ATTECs to degradation of targeted proteins.

Laparoscopic versus open surgery for rectal neuroendocrine tumors: a multicenter real-world study.

BACKGROUND: Owing to the lack of evidence-based medical studies with large sample sizes, the surgical approach for the radical resection of rectal neuroendocrine tumors remains controversial. METHODS: We retrospectively collected the medical records of patients with rectal neuroendocrine tumors who underwent radical resection at 17 large tertiary care hospitals in China between January 1, 2010, and April 30, 2022. All patients were divided into laparoscopic and open surgery groups. After propensity score matching to reduce confounders, the postoperative and oncologic outcomes were compared between the groups. RESULTS: We enrolled 174 patients with rectal neuroendocrine tumors who underwent radical surgery. After random matching, 124 patients were included in the comparison (62, laparoscopic surgery group; 62, open surgery group). The laparoscopic surgery group had fewer complications (14.5% vs. 35.5%, P = 0.007) and superior relapse-free survival (P = 0.048). Subgroup analysis revealed that the laparoscopic surgery group had fewer complications (10.9% vs. 34.7%, P = 0.004), shorter postoperative hospital stays (9.56 ± 5.21 days vs. 12.31 ± 8.61 days, P = 0.049) and superior relapse-free survival (P = 0.025) in the rectal neuroendocrine tumors ≤ 4 cm subgroup. CONCLUSIONS: Laparoscopic surgery was associated with improved postoperative outcomes and oncologic prognosis for patients with rectal neuroendocrine tumors ≤ 4 cm; it can serve as a safe and feasible option for radical surgery of rectal neuroendocrine tumors.

Local Excision Versus Radical Resection for Grade 2 Rectal Neuroendocrine Tumors: A Multicenter Propensity Score-Matched Analysis.

BACKGROUND: Studies on grade 2 rectal neuroendocrine tumors are limited, and the optimal treatment for these tumors is not well established. OBJECTIVE: We aimed to compare the oncologic results of local excision versus radical resection for the treatment of grade 2 rectal neuroendocrine tumors. DESIGN: Retrospective multicenter propensity score-matched study to minimize heterogeneity between groups and focus on the differences between surgery strategies. SETTINGS: Seventeen large-scale Chinese medical centers participated in this study. PATIENTS: A total of 144 patients with pathologically confirmed grade 2 rectal neuroendocrine tumors were retrospectively analyzed. MAIN OUTCOME MEASURES: Cancer-specific survival and relapse-free survival were assessed to compare surgery strategies. RESULTS: A total of 144 patients with grade 2 rectal neuroendocrine tumors were enrolled in this study. Twenty-seven patients underwent endoscopic resection, 55 underwent transanal excision, 50 underwent radical resection, and 12 underwent palliative surgery or biopsy for distant metastasis. Of the 50 patients who underwent radical resection, 30 (60.0%) had clinically positive lymph nodes on the basis of the histopathology results. The optimal cutoff value for tumor size to predict cancer-specific survival was 1.5 cm. In patients with grade 2 rectal neuroendocrine tumors of ≤1.5-cm size, there were no significant differences in cancer-specific survival and relapse-free survival between local excision and radical resection groups ( p > 0.05). In patients with grade 2 rectal neuroendocrine tumors of >1.5-cm size, relapse-free survival was significantly lower in the local excision group than in the radical resection group ( p = 0.04). LIMITATIONS: The nature of retrospective reviews and a relatively short follow-up period are limitations of this study. CONCLUSIONS: Grade 2 rectal neuroendocrine tumors have a nonnegligible rate of lymph node metastasis. Local excision is a feasible choice for tumors of ≤1.5 cm size without metastasis, whereas radical resection is more beneficial in those of >1.5 cm size. See Video Abstract . ESCISIN LOCAL VERSUS RESECCIN RADICAL PARA TUMORES NEUROENDOCRINOS RECTALES GRADO ANLISIS MULTICNTRICO CON PUNTUACIN DE PROPENSIN COINCIDENTE: ANTECEDENTES:Los estudios sobre los tumores neuroendocrinos rectales de grado 2 son limitados y el tratamiento óptimo para estos tumores no está bien establecido.OBJETIVO:Comparar los resultados oncológicos de la escisión local versus la resección radical para el tratamiento de tumores neuroendocrinos rectales grado 2.DISEÑO:Estudio multicéntrico retrospectivo emparejado por puntuación de propensión para minimizar la heterogeneidad entre grupos y centrarse en la diferencia entre estrategias quirúrgicas.ESCENARIO:Diecisiete centros médicos chinos de gran tamaño participaron en este estudio.PACIENTES:Se analizaron retrospectivamente un total de 144 pacientes con tumores neuroendocrinos rectales grado 2 patológicamente confirmados.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron la supervivencia específica del cáncer y la supervivencia libre de recaída para comparar las estrategias quirúrgicas.RESULTADOS:En este estudio se inscribieron un total de 144 pacientes con tumores neuroendocrinos rectales grado 2. Veintisiete pacientes se sometieron a resección endoscópica, 55 a escisión transanal, 50 a resección radical y 12 a cirugía paliativa o biopsia por metástasis a distancia. De los 50 pacientes que se sometieron a resección radical, 30 (60,0%) tenían ganglios linfáticos clínicamente positivos según los resultados histopatológicos. El valor de corte óptimo para el tamaño del tumor para predecir la supervivencia específica del cáncer fue de 1,5 cm. En pacientes con tumores neuroendocrinos rectales grado 2 ≤ 1,5 cm, no hubo diferencias significativas en la supervivencia específica del cáncer y la supervivencia libre de recaída entre los grupos de escisión local y resección radical ( p >0,05). En pacientes con tumores neuroendocrinos rectales grado 2 > 1,5 cm, la supervivencia libre de recaída fue significativamente menor en el grupo de escisión local que en el grupo de resección radical ( p = 0,04).LIMITACIONES:La naturaleza de la revisión retrospectiva y el período de seguimiento relativamente corto son limitaciones de este estudio.CONCLUSIONES:Los tumores neuroendocrinos rectales grado 2 tienen una tasa no despreciable de metástasis en los ganglios linfáticos. La escisión local es una opción factible para tumores ≤ 1,5 cm sin metástasis, mientras que la resección radical es más beneficiosa en aquellos > 1,5 cm. (Traducción-Dr. Felipe Bellolio ).

A New Multi-Branch Convolutional Neural Network and Feature Map Extraction Method for Traffic Congestion Detection.

With the continuous advancement of the economy and technology, the number of cars continues to increase, and the traffic congestion problem on some key roads is becoming increasingly serious. This paper proposes a new vehicle information feature map (VIFM) method and a multi-branch convolutional neural network (MBCNN) model and applies it to the problem of traffic congestion detection based on camera image data. The aim of this study is to build a deep learning model with traffic images as input and congestion detection results as output. It aims to provide a new method for automatic detection of traffic congestion. The deep learning-based method in this article can effectively utilize the existing massive camera network in the transportation system without requiring too much investment in hardware. This study first uses an object detection model to identify vehicles in images. Then, a method for extracting a VIFM is proposed. Finally, a traffic congestion detection model based on MBCNN is constructed. This paper verifies the application effect of this method in the Chinese City Traffic Image Database (CCTRIB). Compared to other convolutional neural networks, other deep learning models, and baseline models, the method proposed in this paper yields superior results. The method in this article obtained an F1 score of 98.61% and an accuracy of 98.62%. Experimental results show that this method effectively solves the problem of traffic congestion detection and provides a powerful tool for traffic management.

Geomagnetic Disturbances and Pulse Amplitude Anomalies Preceding M > 6 Earthquakes from 2021 to 2022 in Sichuan-Yunnan, China.

Compelling evidence has shown that geomagnetic disturbances in vertical intensity polarization before great earthquakes are promising precursors across diverse rupture conditions. However, the geomagnetic vertical intensity polarization method uses the spectrum of smooth signals, and the anomalous waveforms of seismic electromagnetic radiation, which are basically nonstationary, have not been adequately considered. By combining pulse amplitude analysis and an experimental study of the cumulative frequency of anomalies, we found that the pulse amplitudes before the 2022 Luding M6.8 earthquake show characteristics of multiple synchronous anomalies, with the highest (or higher) values occurring during the analyzed period. Similar synchronous anomalies were observed before the 2021 Yangbi M6.4 earthquake, the 2022 Lushan M6.1 earthquake and the 2022 Malcolm M6.0 earthquake, and these anomalies indicate migration from the periphery toward the epicenters over time. The synchronous changes are in line with the recognition of previous geomagnetic anomalies with characteristics of high values before an earthquake and gradual recovery after the earthquake. Our study suggests that the pulse amplitude is effective for extracting anomalies in geomagnetic vertical intensity polarization, especially in the presence of nonstationary signals when utilizing observations from multiple station arrays. Our findings highlight the importance of incorporating pulse amplitude analysis into earthquake prediction research on geomagnetic disturbances.

CX3CR1 modulates SLE-associated glomerulonephritis and cardiovascular disease in MRL/lpr mice.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) often develop multi-organ damages including heart and kidney complications. We sought to better define the underlying mechanisms with a focus on the chemokine receptor CX3CR1. METHODS: We generated Cx3cr1-deficient MRL/lpr lupus-prone mice through backcrossing. We then employed heterozygous intercross to generate MRL/lpr littermates that were either sufficient or deficient of CX3CR1. The mice were also treated with either Lactobacillus spp. or a high-fat diet (HFD) followed by assessments of the kidney and heart, respectively. RESULTS: Cx3cr1-/- MRL/lpr mice exhibited a distinct phenotype of exacerbated glomerulonephritis compared to Cx3cr1+/+ littermates, which was associated with a decrease of spleen tolerogenic marginal zone macrophages and an increase of double-negative T cells. Interestingly, upon correction of the gut microbiota with Lactobacillus administration, the phenotype of exacerbated glomerulonephritis was reversed, suggesting that CX3CR1 controls glomerulonephritis in MRL/lpr mice through a gut microbiota-dependent mechanism. Upon treatment with HFD, Cx3cr1-/- MRL/lpr mice developed significantly more atherosclerotic plaques that were promoted by Ly6C+ monocytes. Activated monocytes expressed ICOS-L that interacted with ICOS-expressing follicular T-helper cells, which in turn facilitated a germinal center reaction to produce more autoantibodies. Through a positive feedback mechanism, the increased circulatory autoantibodies further promoted the activation of Ly6C+ monocytes and their display of ICOS-L. CONCLUSIONS: We uncovered novel, Cx3cr1 deficiency-mediated pathogenic mechanisms contributing to SLE-associated glomerulonephritis and cardiovascular disease.

A Hybrid Recommender System Based on Autoencoder and Latent Feature Analysis.

A recommender system (RS) is highly efficient in extracting valuable information from a deluge of big data. The key issue of implementing an RS lies in uncovering users' latent preferences on different items. Latent Feature Analysis (LFA) and deep neural networks (DNNs) are two of the most popular and successful approaches to addressing this issue. However, both the LFA-based and the DNNs-based models have their own distinct advantages and disadvantages. Consequently, relying solely on either the LFA or DNN-based models cannot ensure optimal recommendation performance across diverse real-world application scenarios. To address this issue, this paper proposes a novel hybrid recommendation model that combines Autoencoder and LFA techniques, termed AutoLFA. The main idea of AutoLFA is two-fold: (1) It leverages an Autoencoder and an LFA model separately to construct two distinct recommendation models, each residing in a unique metric representation space with its own set of strengths; and (2) it integrates the Autoencoder and LFA model using a customized self-adaptive weighting strategy, thereby capitalizing on the merits of both approaches. To evaluate the proposed AutoLFA model, extensive experiments on five real recommendation datasets are conducted. The results demonstrate that AutoLFA achieves significantly better recommendation performance than the seven related state-of-the-art models.

Fixed-Time Stable Neurodynamic Flow to Sparse Signal Recovery via Nonconvex L1-ß2-Norm.

This letter develops a novel fixed-time stable neurodynamic flow (FTSNF) implemented in a dynamical system for solving the nonconvex, nonsmooth model L1-ß2, ß∈[0,1] to recover a sparse signal. FTSNF is composed of many neuron-like elements running in parallel. It is very efficient and has provable fixed-time convergence. First, a closed-form solution of the proximal operator to model L1-ß2, ß∈[0,1] is presented based on the classic soft thresholding of the L1-norm. Next, the proposed FTSNF is proven to have a fixed-time convergence property without additional assumptions on the convexity and strong monotonicity of the objective functions. In addition, we show that FTSNF can be transformed into other proximal neurodynamic flows that have exponential and finite-time convergence properties. The simulation results of sparse signal recovery verify the effectiveness and superiority of the proposed FTSNF.

Extraperitoneal colostomy after laparoscopic abdominoperineal resection using a cannula for tunnel creation through a trocar port.

BACKGROUND: Extraperitoneal colostomy (EPC) after laparoscopic abdominoperineal resection (APR) remains a challenge for surgeons. This study aims to summarize our laparoscopic EPC method and assess its effects versus a transperitoneal colostomy (TPC) for patients with rectal tumors. METHODS: A total of 133 patients with rectal cancer treated with laparoscopic APR between May 2009 and May 2020 were retrospectively reviewed. The clinical data, including demographics, comorbidities, tumor stage, colostomy duration, and complications were compared between the EPC group and the TPC group. RESULTS: The EPC group included 83 patients whose extraperitoneal tunnels were created using a cannula through a trocar port, and the TPC group included 50 patients whose stomata were formed traditionally. There were no differences in colostomy time [(23.1 ± 6) min vs. (21.4 ± 4) min, P = 0.078], number of parastomal dermatitis patients (5 vs. 2, P = 0.916), or number of stomal stenoses (1 vs. 1, P = 0.715) between the EPC and TPC groups. No cases of parastomal hernia developed in the EPC group, whereas 4 patients were diagnosed with a parastomal hernia; the difference between the two groups was statistically significant (P = 0.036). CONCLUSIONS: Laparoscopic EPC have a lower incidence of parastomal hernia than TPC. It is easy and inexpensive to create an extraperitoneal tunnel using a cannula through a trocar port.