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.

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.

Effect of iron nitrate modification on elimination of organic matter from landfill leachate by sludge-based activated carbon.

Sludge-based activated carbons (SACs) prepared from sewage sludge and corn straw, were modified by ferric nitrate, and the unmodified SAC and modified SAC were used as the adsorbing agent to treat the landfill leachate, the elimination capacity for chemical oxygen demand (COD) and organic matter in leachate were studied. Based on this, the physicochemical properties of SACs and the components changes in leachate were analyzed and characterized by X-ray photoelectron spectroscopy and three-dimensional fluorescence spectroscopy. The results showed that under optimal experimental conditions, the elimination capacities of SAC372 for COD, biological oxygen demand over 5 days, and NH4+-N in the leachate were 81.58%, 54.73%, and 69.08%, respectively; while the adsorption capacities of modified SAC for these three substances were 86.25%, 63.51%, and 79.15%, respectively. The ferric nitrate modification improved the ability of SAC to eliminate COD and organic matter from leachate slightly, and made the adsorption occurred easily. The adsorption process of unmodified SAC was dominated by multi-layer adsorption, while the adsorption process of modified SAC was dominated by monolayer adsorption. The mass fraction of Fe (2p) in modified SAC remarkably increased, from 0.70% to 26.01%, organic functional groups certain phase of Fe oxides with different valence states were generated in SAC, which provided a substrate for iron-carbon micro electrolysis. After adsorbed by unmodified SAC and modified SAC adsorption, the total fluorescence intensity of in the leachate increased by 17.01% and 116.84%, respectively. Both two SACs could decompose the humic acid-like substances into aromatic protein organic compounds, and modified SAC could further decompose the soluble microbial byproduct-like substances.

Effects of rhizosphere fungi on the chemical composition of fruits of the medicinal plant Cinnamomum migao endemic to southwestern China.

BACKGROUND: This study examined how rhizosphere fungi influence the accumulation of chemical components in fruits of a small population species of Cinnamomum migao. RESULTS: Ascomycota and Basidiomycota were dominant in the rhizosphere fungal community of C. migao. Pestalotiopsis and Gibellulopsis were associated with α-Terpineol and sabinene content, and Gibellulopsis was associated with crude fat and carbohydrate content. There were significant differences in rhizosphere fungal populations between watersheds, and there was no obvious change between fruiting periods. Gibberella, Ilyonectria, Micropsalliota, and Geminibasidium promoted sabinene accumulation, and Clitocybula promoted α-Terpineol accumulation. CONCLUSION: The climate-related differentiation of rhizosphere fungal communities in watershed areas is the main driver of the chemical composition of C. migao fruit. The control of the production of biologically active compounds by the rhizosphere fungal community provides new opportunities to increase the industrial and medicinal value of the fruit of C. migao.

Status and progress in the treatment for locally resectable progressive gastric cancer and metastatic gastric cancer. / 可切除的局部进展期胃癌及转移性胃癌治疗现状及进展.

For resectable gastric cancer, although radical surgery is still the main treatment, methods of operation and the curative effect of operation are still in the stage of exploration for metastatic gastric cancer. Radiotherapy, chemotherapy and molecular targeted therapy also play an important role in prolonging the survival period of patients with gastric cancer. Postoperative radiotherapy and chemotherapy can prolong the survival time, but for patients with locally advanced gastric cancer, the preoperative radiotherapy and chemotherapy can also further improve the survival period of patients compared with direct operation. In addition, with the development and using of molecular targeted drugs, such as antiangiogenic agents, immunosuppressive drugs and so on, the survival period of patients with gastric cancer has been further extended.

Oncological consequence of emergent resection of perforated colon cancer with complete obstruction after stent insertion as a bridge to surgery.

PURPOSE: Colonic perforation is a life-threatening complication after colonic stent insertion as a bridge to surgery for acute obstruction caused by colorectal cancer. The oncological consequence of colonic perforation after emergent surgical intervention was unknown. The aim of this short communication was to investigate whether or not the perforation and emergent surgery had obviously impact on the peritoneal recurrence and long-term survival of patients. METHODS: Data of the patients who underwent colorectal stenting as a bridge to surgery in 5 years from 2012 to 2017 was collected by the Endoscopical Surgery Group of Hubei. The perforated cases treated by emergent operation were retrospectively analyzed. RESULTS: During 5 years from 2012 to 2017, 116 cases of colorectal stenting as a bridge to surgery had been performed, and 7 patients had perforation after stent placement and treated by emergent surgery, including 1 case of synchronic liver metastasis treated by one-stage metastasectomy. One of the 7 patients died of septic shock after operation, and the remaining patients were followed up for 6-60 months. There was no evidence of abdominal implantation or extra-abdominal metastasis. CONCLUSION: This small case series implicated that colonic perforation after stent insertion for malignant colorectal obstruction treated by emergent surgery might not obviously increase the peritoneal implantation and metastasis.

Overexpression of PARPBP Correlates with Tumor Progression and Poor Prognosis in Hepatocellular Carcinoma.

BACKGROUND: PARP1-binding protein (PARPBP/PARI/C12orf48), a negative regulator of homologous recombination (HR), has been suggested to function as an oncogene in cervical, lung, and pancreatic cancer. OBJECTIVE: To investigate the expression profile of PARPBP and its role in hepatocellular carcinoma (HCC). METHODS: Using data from the Cancer Genome Atlas and Human Protein Atlas databases, PARPBP expression level and its clinical implication in HCC were identified by t test and Chi-square test. The prognostic value of PARPBP in HCC was evaluated by Kaplan-Meier method, Cox regression analysis, and nomogram. Gene set enrichment analysis (GSEA) was used to screen biological pathways correlated with PARPBP expression in HCC. RESULTS: PARPBP was significantly upregulated in HCC tissues compared with normal liver tissues (P < 0.05). High PARPBP expression was significantly associated with elevated serum AFP level, vascular invasion, poor tumor differentiation, and advanced TNM stage (all P < 0.05). Kaplan-Meier analyses suggested that upregulation of PARPBP was correlated with worse overall survival (OS) and recurrence-free survival (RFS) in HCC. Multivariate analyses further confirmed that PARPBP upregulation was an independent indicator of poor OS and RFS (all P < 0.05). The prognostic nomograms based on PARPBP mRNA expression and TNM stage were superior to those based on the TNM staging system alone (all P < 0.05). Besides, PARPBP DNA copy gain and miR-139-5p downregulation were associated with PARPBP upregulation in HCC. GSEA revealed that "cell cycle," "HR," "DNA replication," and "p53 signaling" pathways were enriched in high PARPBP expression group. CONCLUSION: PARPBP may be a promising prognostic biomarker and candidate therapeutic target in HCC.

The Impact of Protein Acetylation/Deacetylation on Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease in which the body's immune system mistakenly attacks healthy cells. Although the exact cause of SLE has not been identified, it is clear that both genetics and environmental factors trigger the disease. Identical twins have a 24% chance of getting lupus disease if the other one is affected. Internal factors such as female gender and sex hormones, the major histocompatibility complex (MHC) locus and other genetic polymorphisms have been shown to affect SLE, as well as external, environmental influences such as sunlight exposure, smoking, vitamin D deficiency, and certain infections. Several studies have reported and proposed multiple associations between the alteration of the epigenome and the pathogenesis of autoimmune disease. Epigenetic factors contributing to SLE include microRNAs, DNA methylation status, and the acetylation/deacetylation of histone proteins. Additionally, the acetylation of non-histone proteins can also influence cellular function. A better understanding of non-genomic factors that regulate SLE will provide insight into the mechanisms that initiate and facilitate disease and also contribute to the development of novel therapeutics that can specifically target pathogenic molecular pathways.

Cutting Edge: Plasmacytoid Dendritic Cells in Late-Stage Lupus Mice Defective in Producing IFN-α.

Plasmacytoid dendritic cells (pDCs) are professional type I IFN producers believed to promote lupus. However, questions exist about whether they function at the same level throughout the course of lupus disease. We analyzed high-purity pDCs sorted from lupus mice. Although pDCs produced a large amount of IFN-α during disease initiation, those sorted from late-stage lupus mice were found to be defective in producing IFN-α. These pDCs expressed an increased level of MHC, suggesting a functional drift to Ag presentation. We examined the potential mechanism behind the defect and identified a novel transcriptional factor, Foxj2, which repressed the expression of several genes in pDCs, but not IFN-α. Dysregulation in pDCs appears to be predisposed, because they exhibited an altered transcriptional profile before the onset of clinical signs. Our results suggest that pDCs do not function the same throughout the disease course and lose the ability to produce IFN-α in late-stage lupus mice.

Chemokines and Chemokine Receptors in the Development of Lupus Nephritis.

Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN.

Diagnosis and Treatment of Acute Mesenteric Ischemia: Clinical Analysis for 40 Cases of the Patients.

OBJECTIVE: To explore the methods of diagnosis and treatment of the patients with acute mesenteric ischemia (AMI). MATERIAL AND METHOD: The present study took place at Department of General Surgery, Xiangyang Central Hospital of Hubei Province, China between January 2002 and December 2013. The clinical data of 40 cases of AMI were analyzed. RESULTS: Among 40 cases of AMI, 38 had to surgical treatment and two had thrombolysis in superior mesenteric artery (SMA) through interventional radiology. Twenty cases died; thus, overall mortality was 50%. Fifteen cases were subjected to surgical or interventional therapy within 16 hours after onset, and all of them survived. Twenty-five cases were subjected to surgical treatments over 16 hours after onset andfive survived. There was significant difference between them (t = 3.4, p = 0.0009). CONCLUSION: The key point to improve survival rate of AMI was early diagnosis and treatment. In the process of treatment, more attention should be paid on recovering blood supply of SMA, and the relationship between total excision of necrotic intestine and reservation offunctional intestine. The operation should be handled properly to reduce the possibility of short bowel syndrome.

TGF-ß1 down-regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence.

The mechanism underlying persistent hepatitis B virus (HBV) infection remains unclear. We investigated the role of innate immune responses to persistent HBV infection in 154 HBV-infected patients and 95 healthy controls. The expression of NKG2D- and 2B4-activating receptors on NK cells was significantly decreased, and moreover, the expression of DAP10 and SAP, the intracellular adaptor proteins of NKG2D and 2B4 (respectively), were lower, which then impaired NK cell-mediated cytotoxic capacity and interferon-γ production. Higher concentrations of transforming growth factor-beta 1 (TGF-ß1) were found in sera from persistently infected HBV patients. TGF-ß1 down-regulated the expression of NKG2D and 2B4 on NK cells in our in vitro study, leading to an impairment of their effector functions. Anti-TGF-ß1 antibodies could restore the expression of NKG2D and 2B4 on NK cells in vitro. Furthermore, TGF-ß1 induced cell-cycle arrest in NK cells by up-regulating the expression of p15 and p21 in NK cells from immunotolerant (IT) patients. We conclude that TGF-ß1 may reduce the expression of NKG2D/DAP10 and 2B4/SAP, and those IT patients who are deficient in these double-activating signals have impaired NK cell function, which is correlated with persistent HBV infection.

Dynamics of gut microbiota in autoimmune lupus.

Gut microbiota has been recognized as an important environmental factor in health, as well as in metabolic and immunological diseases, in which perturbation of the host gut microbiota is often observed in the diseased state. However, little is known on the role of gut microbiota in systemic lupus erythematosus. We investigated the effects of host genetics, sex, age, and dietary intervention on the gut microbiome in a murine lupus model. In young, female lupus-prone mice resembling women at childbearing age, a population with the highest risk for lupus, we found marked depletion of lactobacilli, and increases in Lachnospiraceae and overall diversity compared to age-matched healthy controls. The predicted metagenomic profile in lupus-prone mice showed a significant enrichment of bacterial motility- and sporulation-related pathways. Retinoic acid as a dietary intervention restored lactobacilli that were downregulated in lupus-prone mice, and this correlated with improved symptoms. The predicted metagenomes also showed that retinoic acid reversed many lupus-associated changes in microbial functions that deviated from the control. In addition, gut microbiota of lupus-prone mice were different between sexes, and an overrepresentation of Lachnospiraceae in females was associated with an earlier onset of and/or more severe lupus symptoms. Clostridiaceae and Lachnospiraceae, both harboring butyrate-producing genera, were more abundant in the gut of lupus-prone mice at specific time points during lupus progression. Together, our results demonstrate the dynamics of gut microbiota in murine lupus and provide evidence to suggest the use of probiotic lactobacilli and retinoic acid as dietary supplements to relieve inflammatory flares in lupus patients.