ABSTRACT
RATIONALE: Diffuse intestinal and mesenteric lipomatosis is a rare condition characterized by the overgrowth of adipose tissue in the intestines and mesentery. This case report aims to highlight the rare occurrence of chronic abdominal distention caused by this disease and its unique invasion into the muscle layer, which has not been previously reported. PATIENT CONCERNS: A 36-year-old woman with a 7-year history of abdominal distension was admitted to our hospital's Department of Gastrointestinal Surgery. DIAGNOSE: Abdominal and pelvic computed tomography revealed diffuse small intestinal lipomatosis. INTERVENTIONS: The patient underwent surgery. We performed an open-field ilectomy involving removal of all lipomatous intestines (250 cm). OUTCOMES: During the surgery, diffuse nodular ileal and mesenteric lipomatosis was confirmed, characterized by the presence of multiple nodular lipomas within the submucosal and muscular layers. The surgical intervention involved the resection of 250 cm of the affected ileum, followed by jejunoileal anastomosis. Postoperative pathology confirmed the diagnosis, with lesions observed in both the submucosa and muscle layers. The patient showed significant improvement in symptoms, with normal intestinal function and weight gain observed over a 10-month follow-up period, and no signs of recurrence. LESSONS: Diffuse intestinal and mesenteric lipomatosis can lead to long-term abdominal distension. Additionally, it may be involved in the muscle layer of the intestinal wall. Surgery is the primary treatment option for symptomatic intestinal lipomatosis.
Subject(s)
Lipomatosis , Mesentery , Humans , Female , Adult , Lipomatosis/surgery , Lipomatosis/pathology , Lipomatosis/complications , Lipomatosis/diagnosis , Mesentery/pathology , Mesentery/surgery , Ileal Diseases/surgery , Ileal Diseases/etiology , Ileal Diseases/diagnosis , Ileum/surgery , Ileum/pathology , Tomography, X-Ray Computed , Chronic DiseaseABSTRACT
The activation of PP5 is essential for a variety of cellular processes, as it participates in a variety of biological pathways by dephosphorylating substrates. However, activation of PP5 by small molecules has been a challenge due to its native "self-inhibition" mechanism, which is controlled by the N-terminal TPR domain and the C-terminal αJ helix. Here, we reported the discovery of DDO-3733, a well-identified TPR-independent PP5 allosteric activator, which facilitates the dephosphorylation process of downstream substrates. Considering the negative regulatory effect of PP5 on heat shock transcription factor HSF1, pharmacologic activation of PP5 by DDO-3733 was found to reduce the HSP90 inhibitor-induced heat shock response. These results provide a chemical tool to advance the exploration of PP5 as a potential therapeutic target and highlight the value of pharmacological activation of PP5 to reduce heat shock toxicity of HSP90 inhibitors.
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BACKGROUND: This study was designed to explore whether hsa_circ_0070440 was dysregulated in prostate cancer (PCa), and assess the effects of hsa_circ_0070440 alteration on PCa prognosis and cell function. METHODS: The expression levels of hsa_circ_0070440 were assessed in PCa tissues and cell lines. After the classification of patients with PCa based on mean hsa_circ_0070440 level in 138 cases, Chi-square test and survival analyses (Kaplan-Meier method and multivariable Cox proportional hazards analysis) were performed to assess the predictive value of hsa_circ_0070440 in treatment failure (TTF), time to PSA progression (TTPP) and overall survival time. To examine the function of hsa_circ_0070440 in PCa cells, 22Rv1 and C4-2B cells were used for CCK-8 proliferation and Transwell migration assays. Hsa_circ_0070440- and TXNDC5-specific bindings with miR-382/383-5p were validated by bioinformatic analysis and luciferase gene reporter assay. RESULTS: An increased expression of hsa_circ_0070440 was found in PCA tissues and cell lines, associated with clinical T stage (p=0.021) and lymph node metastasis. Hsa_circ_0070440 predicted poor overall survival, TTPP, and TTF, acting as independent prognostic factors for overall survival, TTPP, and TTF in patients with PCa. Knockdown of hsa_circ_0070440 inhibited cell proliferation and migration in vitro. Furthermore, hsa_circ_0070440 could sponge miR-382/383-5p. TXNDC5 was a common target gene for miR-382/383-5p in PCa cells. CONCLUSION: This study demonstrated that hsa_circ_0070440 can predict the prognosis of PCa patients. Hsa_circ_0070440 can facilitate the proliferation and migration of PCa cells, possibly by sponging miR-382/383-5p.
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One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
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Urban sustainability is a key to achieving the UN sustainable development goals (SDGs). Secure and efficient provision of food, energy, and water (FEW) resources is a critical strategy for urban sustainability. While there has been extensive discussion on the positive effects of the FEW nexus on resource efficiency and climate impacts, measuring the extent to which such synergy can benefit urban sustainability remains challenging. Here, we have developed a systematic and integrated optimization framework to explore the potential of the FEW nexus in reducing urban resource demand and greenhouse gas (GHG) emissions. Demonstrated using the Metropolis Beijing, we have identified that the optimized FEW nexus can reduce resource consumption and GHG emissions by 21.0 and 29.1%, respectively. These reductions come with increased costs compared to the siloed FEW management, but it still achieved a 16.8% reduction in economic cost compared to the business-as-usual scenario. These findings underscore the significant potential of FEW nexus management in enhancing urban resource efficiency and addressing climate impacts, while also identifying strategies to address trade-offs and increase synergies.
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Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.
Subject(s)
Adenine Nucleotide Translocator 2 , Mitochondria , Mitochondrial Membranes , RNA, Double-Stranded , Animals , Adenine Nucleotide Translocator 2/metabolism , Adenine Nucleotide Translocator 2/genetics , Humans , RNA, Double-Stranded/metabolism , Mitochondria/metabolism , Mitochondrial Membranes/metabolism , Mice , Immunity, Innate , RNA Transport , HEK293 Cells , Mice, Inbred C57BLABSTRACT
BACKGROUND: Dyslipidemia is frequently present in patients with diabetes. The associations of remnant cholesterol and mortality remains unclear in patients with diabetes. AIM: To explore the associations of remnant cholesterol with all-cause and cardiovascular mortality in patients with diabetes. METHODS: This prospective cohort study included 4740 patients with diabetes who participated in the National Health and Nutrition Examination Survey from 1999 through 2018. Remnant cholesterol was used as the exposure variable, and all-cause and cardiovascular mortality were considered outcome events. Outcome data were obtained from the National Death Index, and all participants were followed from the interview date until death or December 31, 2019. Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes, in which remnant cholesterol was modeled as both a categorical and a continuous variable. Restricted cubic splines (RCSs) were calculated to assess the nonlinearity of associations. Subgroup (stratified by sex, age, body mass index, and duration of diabetes) and a series of sensitivity analyses were performed to evaluate the robustness of the associations. RESULTS: During a median follow-up duration of 83 months, 1370 all-cause deaths and 389 cardiovascular deaths were documented. Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality [hazard ratio (HR) 95% confidence interval (CI): 0.66 (0.52-0.85)]; however, when remnant cholesterol was modeled as a continuous variable, it was associated with increased risks of all-cause [HR (95%CI): 1.12 (1.02-1.21) per SD] and cardiovascular [HR (95%CI): 1.16 (1.01-1.32), per SD] mortality. The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality. Subgroup and sensitivity analyses did not reveal significant differences from the above results. CONCLUSION: In patients with diabetes, higher remnant cholesterol was associated with increased risks of all-cause and cardiovascular mortality, and diabetes patients with slightly higher remnant cholesterol (0.68-1.04 mmol/L) had a lower risk of all-cause mortality.
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Background: Specifically blocking HSP90-CDC37 interaction is emerging as a prospective strategy for cancer therapy. Aim: Applying a kinase pseudopeptide rationale to the discovery of HSP90-CDC37 protein-protein interaction (PPI) inhibitors. Methods: Pseudosubstrates were identified through sequence alignment and evaluated by biolayer interferometry assay, co-immunoprecipitation assay and antiproliferation assay. Results: TAT-DDO-59120 was identified to disrupt HSP90-CDC37 PPI through directly binding to HSP90, both extracellularly and intracellularly. In addition, the identified peptide showed ideal antiproliferative activity against the colorectal cancer cell HCT116 (IC50 = 12.82 µM). Conclusion: Compared with the traditional method of screening a large compound library to identify PPI inhibitors, this method is rapid and efficient with strong purpose, which provides a novel strategy for designing HSP90-CDC37 PPI inhibitors.
Subject(s)
Antineoplastic Agents , Cell Cycle Proteins , Chaperonins/chemistry , Chaperonins/metabolism , Molecular Chaperones/metabolism , HSP90 Heat-Shock Proteins/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Peptides/pharmacology , Peptides/metabolism , Protein BindingABSTRACT
TECHNIQUE: (1) A four-pointed star-shaped incision was made to separate the skin around the stoma intestine. (2) The stoma intestine was resected, and side-to-side or end-to-side anastomosis was performed to restore the continuity of the intestine. (3) The peritoneum and rectus sheath should be closed using continuous full-thickness sutures. (4) The subcutaneous fat layer and dermis layer should be sutured using purse-string sutures. Two holes should be made in the center of the sutured area. (5) The cross should be sutured intermittently on all four sides using 1-2 stitches. (6) A rubber strip should be placed in the center of the small hole. RESULTS: The presence of a small hole in the center of the incision and the use of a rubber strip for drainage facilitate early fluid drainage. The design of a cross-stitched skin incision helps reduce local tension. CONCLUSION: The modified cross-suture technique may reduce postoperative incision infections and associated pain, which is a suitable incision treatment method for loop stoma reversal.
Subject(s)
Abdominal Wall , Surgical Stomas , Humans , Rubber , Suture Techniques , Surgical Wound Infection , SuturesABSTRACT
LncRNAs are abnormally expressed in a variety of cancers and play unique roles in therapy. Based on this, the prognostic value of lncRNA LINC01018 in prostate cancer was discussed in this study. LINC01018 was underexpressed in prostate cancer tissues and cells, while miR-182-5p was elevated (***p < 0.001). Overexpression of LINC01018 may inhibit the progression of prostate cancer by targeting miR-182-5p. This study revealed that upregulated LINC01018 may prolong the overall survival of patients with prostate cancer (log-rank p = 0.042), and LINC01018 may become a prognostic biomarker for patients with prostate cancer, which brings a new direction for the treatment of patients.
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Natrium superionic conductor (NASICON) is a promising solid-state electrolyte because of its high stability under air as well as its safety. Doping is an effective way to improve its ionic conductivity, but there is limited information about the explanation of the doping sites. In this work, Al-doped NASICONs are designed. When Al doping is 0.3 (NAl0.3ZSP), the ionic conductivity is the highest and is 5.08 × 10-5 S cm-1 at 30 °C, which is 3.3 times that of undoped NASICON. NAl0.3ZSP consists of a NASICON structure (monoclinic and rhombohedral phases), an amorphous glassy phase, and Na3PO4 impurities. After Al doping, more Si/P sites are occupied by Al; thus, the ratio of Na3PO4 impurities increases. Na3PO4 at the grain boundary is beneficial for grain boundary resistance decrease, contributing to the decrease of the total resistance. Our work first provides a detailed explanation of doped-Al sites and interprets their effects on ionic conductivity.
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The elucidation of protein function and its exploitation in bioengineering have greatly advanced the life sciences. Protein mining efforts generally rely on amino acid sequences rather than protein structures. We describe here the use of AlphaFold2 to predict and subsequently cluster an entire protein family based on predicted structure similarities. We selected deaminase proteins to analyze and identified many previously unknown properties. We were surprised to find that most proteins in the DddA-like clade were not double-stranded DNA deaminases. We engineered the smallest single-strand-specific cytidine deaminase, enabling efficient cytosine base editor (CBE) to be packaged into a single adeno-associated virus (AAV). Importantly, we profiled a deaminase from this clade that edits robustly in soybean plants, which previously was inaccessible to CBEs. These discovered deaminases, based on AI-assisted structural predictions, greatly expand the utility of base editors for therapeutic and agricultural applications.
Subject(s)
Gene Editing , Proteins , Proteins/metabolism , Cytidine Deaminase/genetics , Cytidine Deaminase/metabolism , DNA , CRISPR-Cas Systems , Cytosine/metabolismABSTRACT
The ecosystem services of the Qinghai-Tibet Plateau have been hot topics in recent decades due to their unique value, and the region's sensitivity to climate change and human activities is considered to be of major importance. However, few studies have focused on the variations of ecosystem services in response to traffic activities and climate change. This study applied different ecosystem service models, along with the buffer analysis, local correlation and regression analysis to quantitatively analyze the spatiotemporal variations of carbon sequestration, habitat quality, and soil retention, further detected the climatic and traffic influences in the transport corridor region of the Qinghai-Tibet Plateau from 2000 to 2020. The obtained results showed the following: (1) The carbon sequestration and soil retention increased over time, while the habitat quality decreased during the railway construction period; in addition, the variations of ecosystem services between the two periods exhibited substantial spatial differences. (2) The distance trends of ecosystem service variations were similar for the railway and the highway corridors, and the positive ecosystem service trends were mainly observed within 2.5 km and 2 km of railway and highway corridors, respectively. (3) The impacts of climatic factors on ecosystem services were predominantly positive; however, temperature and precipitation displayed contrasting distance trends in their impacts on carbon sequestration. (4) The types of frozen ground and locations away from the railway or highway were the combined factors affecting the ecosystem services, among which carbon sequestration was negatively influenced by the distance from the highway in the continuous permafrost areas. It can be speculated that rising temperatures caused by climate change may intensify the decline of carbon sequestration in the continuous permafrost areas. This study provides guidance on ecological protection strategies for future expressway construction projects.
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Urbanization and globalization are changing the conventional constraints of seasonality and geography on food consumption, such as that of fresh cherries. The rising demand for year-round cherry consumption in China is currently satisfied by open-field, greenhouse-produced, and imported products. This study conducted a spatial-temporal life cycle evaluation of the environmental performance of cherry consumption behaviors during different seasons of the year. Moreover, based on the definitions of global and local seasonality, the additional environmental costs of out-of-season cherry consumption were estimated. Results show that seasonality was an important factor affecting the environmental burdens of cherry consumption. Eating cherries imported from Chile by air in October resulted in the highest greenhouse gas (GHG) emissions of 6.38 kg CO2-eq/kg, while eating domestic open-field cherries during May to July (the natural harvest season) was a relatively environmentally beneficial option. The total cherry consumption in China in 2019 generated GHG emissions of 126.99 × 104 t CO2-eq. Under the definitions of global and local seasonality, the out-of-season consumption led to additional environmental costs of 57.59 × 104 and 85.67 × 104 t CO2-eq, accounting for 45.35% and 67.46% of total emissions, respectively. Furthermore, the time-environment trade-off effect of cherry consumption illustrates the higher environmental costs are exchanged for satisfying the appetite for out-of-season fresh foods. Our findings emphasize the meaningful implications for developing a sustainable consumption pattern for all stakeholders involved in the entire food chain.
Subject(s)
Appetite , Greenhouse Gases , Carbon Dioxide/analysis , China , Seasons , Greenhouse EffectABSTRACT
A novel ionic conjugated polymer fluorescent probe (IP) containing fluorenyls and imines was synthesized through a simple condensation method for the rapid detection of Cu2+. The probe exhibited a selective quenching response toward Cu2+over other common metal ions in phosphate-buffered saline (PBS) at a pH of 7. Moreover, the fluorescence intensity ofIPwas linearly proportional to the concentration of Cu2+when it ranged from 1 to 10µM, and the limit of detection for Cu2+was 0.45µM. Furthermore, the quenched fluorescence ofIPby Cu2+was recovered after adding amino acids or ethylenediaminetetraacetic acid (EDTA), indicating that the probe could be recycled and is promising to reduce the detection cost of Cu2+in real samples.
Subject(s)
Copper , Fluorescent Dyes , Fluorescent Dyes/chemistry , Copper/chemistry , Polymers , Ions , Water/chemistryABSTRACT
Although COVID-19 lockdown policies have improved air quality in numerous countries, there is a lack of empirical evidence on the extent to which recovery has resulted in air pollution rebound, and the differences and similarities among regions' recovery modes during the period of easing COVID-19 restrictions. Here, we used daily air quality data and the recovery index constructed by a city-pair inflow index for 119 cities in China to quantify the impact of recovery on air pollution from March 2 to October 30, 2020. Findings show that recovery has significantly increased air pollution. When the recovery level increased by 10 %, the concentration of PM2.5, SO2, and NO2 respectively deteriorated by 1.10, 0.33, 1.25 µg/m3, and the average growth rates of three air pollutants were about 3 %-6 %. Moreover, we used the counterfactual framework and time series clustering with wavelet transform to cluster the rebound trajectory of air pollution for 17 provinces into five recovery modes. Results show that COVID-19 has further intensified regional differentiations in economic development ability and green recovery trend. Three northwestern provinces dependent on their resource endowments belong to energy-intensive recovery mode, which have experienced a sharp rebound of air pollution for two months, thereby making green recovery more challenging to achieve. Three regions with a diversified industrial structure are in industrial-restructuring recovery mode, which has effectively returned to a normal level through adjusting industrial structure and technological innovation. Owing to local policies and the outbreak of COVID-19 in other countries, six provinces in policy-oriented and international trade-oriented recovery modes have not fully recovered to the level without COVID-19 until October 2020. The result highlights the importance of diversifying industrial structure, technological innovation, policy flexibility and industrial upgrading for different recovery modes to achieve long-term green recovery in the future.
Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Air Pollutants/analysis , Air Pollution/analysis , Air Pollution/prevention & control , COVID-19/epidemiology , China/epidemiology , Cities , Commerce , Communicable Disease Control , Environmental Monitoring , Humans , Internationality , Particulate Matter/analysisABSTRACT
Oxygen activation, including oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), is at the heart of many important energy conversion processes. However, the activation mechanism of Ba-containing perovskite materials is still ambiguous, because of the complex four-electron transfer process on the gas-solid interfaces. Here, we directly observe that BaO and BaO2 segregated on Ba-containing material surface participate in the oxygen activation process via the formation and decomposition of BaO2. Tens of times of increase in catalytic activities was achieved by introducing barium oxides in the traditional perovskite and inert Au electrodes, indicating that barium oxides are critical for oxygen activation. We find that BaO and BaO2 are more active than the B-site of perovskite for ORR and OER, respectively, and closely related to the high activity of Ba-containing perovskite.
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Micro-image strain sensing (MISS) is an innovative technology to measure strain within a measurement range of ±8300 microstrains. It has been proved to be effective and satisfy all requirements in the field of structural health monitoring. However, there is still room for improvement and extend the range of measurement. In this paper, an improved method is proposed to increase the measurement range of strain and displacement. Moreover, various tests were conducted to verify the efficiency of the improved method. The results showed that the modified method is efficient and accurate and can be readily used to extend the measurement range of both strain and displacement. This research will likely help stimulate the development of multifunctional sensors to obtain abundant useful information about structures in the field of structural health monitoring. It will allow measuring strain and displacement, which require different levels of accuracy, using one unified sensor.