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Abstract Stroke is a major cause of death and disability among adults in China, and an efficient rehabilitation strategy has been an urgent demand for post-stroke rehabilitation. The non-invasive brain stimulation (NBS) can modulate the excitability of the cerebral cortex and provide after-effects apart from immediate effects to regain extremity motor functions, whereas robotic therapy provides high-intensity and long-duration repetitive movements to stimulate the cerebral cortex backward. The combined strategy of the two techniques is widely regarded as a promising application for stroke patients with dyskinesia. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) are important methods of NBS. Their recovery principles, stimulation parameters, and clinical applications have been summarized. The combined treatments of rTMS/tDCS and robotic therapy are analyzed and discussed to overcome the application barriers of the two techniques. The future development trend and the key technical problems are expounded for the clinical applications.

Abstract Background Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. Methods In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. Results Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3β and resulted in increased β-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. Conclusions OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.

Abstract Long non-coding RNAs (lncRNAs) are abundant in plants, however, their regulatory roles remain unclear in most biological processes, such as response in salinity stress which is harm to plant production. Here we show a lncRNA in Medicago truncatula identified from salt-treated Medicago truncatula is important for salinity tolerance. We name the lncRNA LAL, L ncRNA A NTISENSE to M. truncatula L IGHT-HARVESTING CHLOROPHYLL A/B BINDING (MtLHCB) genes. LAL is an antisense to four consecutive MtLHCB genes on chromosome 6. In salt-treated M. truncatula, LAL is suppressed in an early stage but induced later; this pattern is opposite to that of the four MtLHCBs. The lal mutants show enhanced salinity tolerance, while overexpressing LAL disrupts this superior tolerance in the lal background, which indicates its regulatory role in salinity response. The regulatory role of LAL on MtLHCB1.4 is further verified by transient co-expression of LAL and MtLHCB1.4-GFP in tobacco leaves, in which the cleavage of MtLHCB1.4 and production of secondary interfering RNA is identified. This work demonstrates a lncRNA, LAL, functioning as a regulator that fine-tunes salinity tolerance via regulating MtLHCB1s’ expression in M. truncatula.

Abstract Recent research underscores the significance of the nervous system in tumor progression. Nonetheless, understanding the intricate roles of nerves in gastric tumorigenesis remains limited. Our study aims to elucidate nerve alterations, associated key genes, and signaling pathways during gastric tumorigenesis. We enroll 257 patients with gastric precancerous lesions (GPLs) from four national cohorts. Utilizing immunohistochemistry and digital analysis, we quantified the densities of sympathetic and parasympathetic nerves, as well as Schwann cells in patient slides. We collected three mRNA expression profiles of GPL samples from the gene expression omnibus database and assessed them for nerve expression signatures, differentially expressed genes, enriched pathways, and the immune microenvironment. Parasympathetic nerve and Schwann cell densities display a progressive increase, while sympathetic nerve exhibits an inverse trend along the precancerous spectrums. Notably, CD8+ T cells, natural killer cells, and antigen‐presenting cells (APC) co‐inhibition decrease, while epithelial‐mesenchymal transition increases significantly from early to late premalignancy. Several key nerve‐regulating genes (NTRK3, MYBL2, NRP1, BCL2, CCND1, VEGFA, PLXNA2, ADRB2), and pathways (mitogen‐activated protein kinase [MAPK]/ERK, PI3K/AKT, Wnt) emerge as potential contributors to precancerous progression. Our study reveals a dynamic relationship between sympathetic and parasympathetic nerves, characterized by a gradual increase in parasympathetic nerve and Schwann cell density, contrasting with an inverse trend in sympathetic nerve across precancerous spectrums. Targeting the interaction between tumor cells and nerves, including sympathetic and parasympathetic nerves, has emerged as a promising strategy for the prevention and treatment of gastric cancer.

Abstract Apple valsa canker caused by the Ascomycete fungus Valsa mali is one of the most serious diseases of apple, resulting in huge economic losses in the apple-growing area of China. Previous study found that the pathogen could acidify the infected tissues to make lower ambient pH (from 6.0 to 3.5) for their successfully colonization. The pH signaling transcription factor VmPacC is required for acidification of its environment and for full virulence in V. mali. It is known that the functional cooperation of proteins secreted by V. mali plays pivotal role in its successful colonization of host plants. In this study, we used tandem mass tag (TMT) labeling coupled with LC-MS/MS-based quantitative proteomics to analyze the VmPacC-mediated pH regulation in V. mali, focusing on differentially expressed proteins (DEPs). We identified 222 DEPs specific to VmPacC deletion, and 921 DEPs specific to different pH conditions (pH 6.0 and 3.4). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these DEPs were mainly involved in pathways associated with carbon metabolism, biosynthesis of antibiotics, citrate cycle (TCA cycle), glycolysis/gluconeogenesis, glutathione metabolism, ribosomes, and pentose phosphate pathways. Additionally, we identified 119 DEPs that were shared among the VmPacC deletion mutant and different pH conditions, which were mainly related to energy metabolism pathways, providing the energy required for the hyphal growth and responses to environmental stresses. A protein-protein interaction (PPI) network analysis indicated that most of the shared proteins were mapped to an interaction network with a medium confidence score of 0.4. Notably, one uncharacterized protein (KUI69106.1), and two known proteins (heat shock protein 60 (KUI73579.1), aspartate aminotransferase (KUI73864.1)) located in the core of the network were highly connected (with ≥ 38 directed edges) with the other shared DEPs. Our results suggest that VmPacC participates in the pathogen’s regulation to ambient pH through the regulation of energy metabolism pathways such as the glycolysis/gluconeogenesis pathway and TCA cycle. Finally, we proposed a sophisticated molecular regulatory network to explain pH decrease in V. mali. Our study, by providing insights into V. mali regulating pH, helps to elucidate the mechanisms of host acidification during pathogen infection.

Fish are the main source of long-chain polyunsaturated fatty acids (LC-PUFA), in particular docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3), which are nutritionally valuable to humans. Moreover, lipid and fatty acid distribution in fish tissues are highly diverse across species. The lipid distribution pattern across tissues determines fatty acid profile, one of the product quality indicators of fish. However, this diversity of lipid distribution and fatty acid profile is not fully known, although several studies have been conducted to compare the nutritive composition of muscle in different fish species in both freshwater and marine environments. This study aimed to comprehensively investigate the lipid distribution and fatty acid profile, as well as the somatic indexes and approximate composition of five benthic marine fish species, namely yellow anglerfish (Lophius litulon), flathead (Platycephalus indicus), eelpout (Zoarces viviparus), East Asian flatfish (Pleuronichthys cornutus), and zebra sole (Zebrias zebrinus). Fishes were purchased from the 15th Street Seafood Market of Qingdao, which were stored on ice since captured in an inshore fishery in Qingdao (located at 119°30'–121°00'E and 35°35'–37°09'N), and then delivered to the market from the fishing harbor in the same morning. After purchase, fishes were kept on ice and immediately taken to the laboratory. The experimental design consisted of nine fish of each species bulked in groups of three, comprising three replicates. First, the total weight and length of each fish were measured, and the liver and viscera weight were recorded to calculate the viscerosomatic index (VSI), hepatosomatic index (HSI), and condition factor (CF). Subsequently, samples of muscle, liver, brain, eye, skin, subcutaneous adipose tissue around fins (only for East Asian flatfish and zebra sole), and intraperitoneal adipose tissue (only for flathead) were collected for lipid and fatty acid analysis. The dorsal muscle sampling position is behind the head on the right body side. The ventral muscle samples were collected under the dorsal muscle sampling spot. The proximate composition analysis of the dorsal muscle, ventral muscle, and liver (three individual samples per group) was performed according to the Association of Official Analytical Chemists standard methods. For the moisture assay, samples were oven-dried at 105 ℃ until they achieved a constant weight. The protein content was assayed by measuring nitrogen (N × 6.25) using the Soxhlet method, the lipids were analyzed using the Soxhlet method (petroleum ether extraction), and the ash by incineration at 550 ℃. The fatty acid compositions of all tissues were analyzed with gas chromatography (GC-2010, Shimadzu, Japan). The results showed that the flat body type of flatfish determines that the gut in these fish species cannot store high lipid contents in the liver or intraperitoneal adipose tissues. Like other flatfish, East Asian flatfish and zebra sole had lower HSI and VSI. In contrast, the HSI and VSI of yellow anglerfish and flathead were associated with high lipid contents in the gut. Additionally, the lipid distribution across tissues indicated that yellow anglerfish and flathead predominantly stored lipid in the liver and intraperitoneal adipose tissue, respectively. The muscle lipid content of all the five species was low, especially for yellow anglerfish and zebra sole (0.3%–0.4%). Yellow anglerfish, flathead, and East Asian flatfish had higher liver lipid content (19%–29%) than zebra sole and eelpout (4%–5%). Yellow anglerfish and flathead store lipid predominantly in the liver and intraperitoneal adipose tissue, respectively. The n-3 LC-PUFA content, especially DHA, in the muscle of yellow anglerfish was significantly higher than that of other species. The yellow anglerfish dorsal muscle also had the highest 18:1n-9 content. The relative abundances of different monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA) in different fish species indicate a preference for energy storage and lipid mobilization. The most distinct fatty acid characteristics of the dorsal muscle of eelpout were low 16:0 content and high EPA content. For liver fatty acids, flathead and East Asian flatfish had significantly high MUFA contents, such as 18:1n-9, but their DHA contents were low. High DHA, 20:4n-6, and 22:5n-3 contents were consistently observed in nearly all yellow anglerfish, eelpout, and East Asian flatfish tissues, respectively, while low EPA content was observed for all of them. Among all five fish species, eelpout had a much higher ARA content than the other species in nearly all tissues. This could be due to the high ARA level in the food sources, namely algae. Yellow anglerfish had significantly high n-3 LC-PUFA content and thus high fatty acids nutritional value. This study revealed that even though these fishes are all benthic species, there are great differences in lipid and fatty acid composition among them.

This study aimed to evaluate the effects of combined replacement of fishmeal (FM) and fish oil (FO) with poultry byproduct meal (PBM) and mixed oil (MO, poultry oil: coconut oil = 1 : 1) on growth performance, body composition and muscle quality of tiger puffer (Takifugu rubripes). Fish with an average initial body weight of 14.29 g were selected for the feeding experiment. FM accounting for 0%, 5%, and 10% of the diet was replaced by PBM. For each grade of FM replacement, 5% FO or MO was used as added oil. The six experimental diets were designated as FO-FM, MO-FM, FO-5PBM, MO-5PBM, FO-10PBM, and MO-10PBM, respectively. Each treatment was performed in triplicate with 30 fish per replicate. The feeding period was 45 days. There was no significant difference in growth performance among the groups. Dietary supplementation of both PBM and MO had marginal effects on whole-fish proximate composition, except that dietary MO supplementation significantly increased the liver moisture content. In serum, there were no significant differences in contents of triglyceride, total cholesterol, total bile acid, and protein carbonyl among groups, but the malondialdehyde content was reduced by MO. The fatty acid composition in fish mirrored those in the diets, but the omega-3 sparing effects of saturated and monounsaturated fatty acid in MO can still be observed. Dietary PBM and MO had marginal effects on free amino acid composition and texture of fish muscle, but exerted complicated effects on the muscle volatile flavor compound composition. In conclusion, combined fishmeal (10% of the diet) and fish oil (5% of the diet) replacement with poultry byproduct and mixed oil (poultry oil + coconut oil) had no adverse effects on the growth performance and body proximate composition of farmed tiger puffer. However, these replacements changed the muscle flavor compound profile.

Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker that can define the risk of recurrence after curative-intent surgery for patients with colorectal cancer (CRC). However, beyond the predictive power of postoperative ctDNA detection, the efficacy and potential limitations of ctDNA detection urgently need to be fully elucidated in a large cohort of CRC. Objectives: To define potentially cured CRC patients through ctDNA monitoring following surgery. Design: A prospective, multicenter, observational study. Methods: We enrolled 309 patients with stages I–IV CRC who underwent definitive surgery. Tumor tissues were sequenced by a custom-designed next-generation sequencing panel to identify somatic mutations. Plasma was analyzed using a ctDNA-based molecular residual disease (MRD) assay which integrated tumor-genotype-informed and tumor-genotype-naïve ctDNA analysis. The turnaround time of the assay was 10–14 days. Results: Postoperative ctDNA was detected in 5.4%, 13.8%, 15%, and 30% of patients with stage I, II, III, and IV disease, respectively, and in 17.5% of all longitudinal samples. Patients with positive postsurgery MRD had a higher recurrence rate than those with negative postsurgery MRD [hazard ratio (HR), 13.17; p < 0.0001], producing a sensitivity of 64.6%, a specificity of 94.8%, a positive predictive value (PPV) of 75.6%, and a negative predictive value (NPV) of 91.5%. Furthermore, patients with positive longitudinal MRD also had a significantly higher recurrence rate (HR, 14.44; p < 0.0001), with increased sensitivity (75.0%), specificity (94.9%), PPV (79.6%), and NPV (93.4%). Subgroup analyses revealed that adjuvant therapy did not confer superior survival for patients with undetectable or detectable MRD. In addition, MRD detection was less effective in identifying lung-only and peritoneal metastases. Conclusion: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and microsatellite instability status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.

Yadong trout (Salmo trutta fario), the only salmonid fish in the Tibetan Plateau, is a national agricultural product with geographical indications in Yadong. The development of Yadong trout aquaculture has significant implications for local farmers. However, no study has yet investigated the nutrient requirements of this fish. This study aimed to analyze the proximate amino acid, and fatty acid composition of various tissues of wild and farmed Yadong trout, in order to provide a reference for the evaluation of fish fillets and the formulation of optimal feed. Ten wild fish captured in the Yadong River, and 10 fish farmed with formulated feed in Yadong Industry Park were used in this study. The farmed fish were F1 generation wild broodstock captured in the Yadong River and fed formulated feeds throughout their lifetime. The body length of wild Yadong trout was in the range of 13.4~28.7 cm, and the body weight was in the range of 38.48~346.85 g. The body length and body weight of farmed Yadong trout were in the range of 16.4~24.5 cm and 78.39~275.29 g, respectively. Frozen samples were transported to the laboratory by flight. The proximate composition of whole fish, muscle, and liver; fatty acid composition of whole fish and various tissues including muscle, liver, intestine, brain, and eye; as well as amino acid composition of whole fish, muscle, and liver were analyzed. The fatty acid composition (expressed as % total fatty acids) and amino acid composition (expressed as % dry matter basis) were assayed using gas chromatography and an automatic amino acid analyzer, respectively. In addition, t-tests were performed for independent samples; results are expressed as the mean ± standard deviation. The results showed that wild fish had lower condition factors but higher moisture and ash content than farmed fish. Wild fish muscle had lower crude lipid content but higher moisture content than farmed fish. The whole-body protein and lipid contents, as well as the proximate composition of the liver, were not significantly different between wild and farmed fish (P > 0.05). The contents of saturated fatty acids (mainly C16:0 and C18:0) and n-3 polyunsaturated fatty acid (PUFA) in whole fish, muscle, and liver were significantly higher (P < 0.05), whereas contents of monounsaturated fatty acids (MUFA) (mainly C16:1n-7 and C18:1n-9) and n-6 PUFA (mainly C18:2n-6) were significantly lower in wild Yadong trout than in farmed Yadong trout (P < 0.05). EPA and C20:4n-6 in whole fish, muscle, and liver, as well as DHA in the muscle of wild Yadong trout were significantly higher than those in farmed Yadong trout (P < 0.05). In the intestine of wild Yadong trout, the contents of C14:0, C16:0, C18:0, C16:1n-7, C20:5n-3, and C22:5n-3 were significantly higher (P < 0.05), while those of C18:1n-9 and C18:2n-6 were significantly lower (P < 0.05) than in the farmed fish. In the brain of wild Yadong trout, the contents of C16:1n-7, C20:5n-3, and C22:5n-3 were significantly higher (P < 0.05), while the contents of C18:1n-9 and C20:2n-6 were significantly lower (P < 0.05) than those of farmed fish. In the eyes of wild Yadong trout, the contents of C14:0, C16:0, and C18:0, C16:1n-7, C20:1n-9, C20:2n-6, C20:4n-6, C20:5n-3, and C22:5n-3 were significantly higher (P < 0.05), while the contents of C18:1n-9, C22:1n-9, C24:1n-9, C18:2n-6, and C18:3n-3 were significantly lower (P < 0.05) than those of farmed Yadong trout. The total essential amino acid content in wild fish was significantly higher than that in farmed fish. The contents of threonine, valine, phenylalanine, lysine, and glycine in the muscle of wild fish were significantly higher (P < 0.05) than those in farmed fish, while no significant difference (P > 0.05) was observed in other amino acids. These results indicate that wild Yadong trout were leaner than farmed trout in terms of muscle lipid content. For trout, which are mainly consumed fresh, this trait may make farmed Yadong trout more acceptable than wild trout. However, in terms of fatty acid composition and amino acids, the wild Yadong trout seemed to be more acceptable than farmed trout. In particular, n-3 PUFA content is an important nutritional trait in fish fillets. The wild Yadong trout had higher n-3 PUFA contents than the farmed trout. Thus, the fish oil in the feeds of Yadong trout should not be omitted, considering that fish chemical composition generally reflects that of their diets. In addition, the price of alternative oils such as soybean oil is no longer low; the use of lipid sources in the diets of Yadong trout should be reviewed. Similarly, the essential amino acid content in wild Yadong trout was higher than that in the farmed trout, suggesting that the protein sources should be reviewed, and a certain level of fish meal should be guaranteed. In conclusion, the results of this study indicate that the formulated feeds of Yadong trout need to be further optimized.

Physics-informed DeepONet (PI_DeepONet) is utilized for the reconstruction task of structural displacement based on measured strain. For beam and plate structures, the PI_DeepONet is built by regularizing the strain–displacement relation and boundary conditions, referred to as geometric differential equations (GDEs) in this paper, and the training datasets are constructed by modeling strain functions with mean-zero Gaussian random fields. For the GDEs with more than one Neumann boundary condition, an algorithm is proposed to balance the interplay between different loss terms. The algorithm updates the weight of each loss term adaptively using the back-propagated gradient statistics during the training process. The trained network essentially serves as a solution operator of GDEs, which directly maps the strain function to the displacement function. We demonstrate the application of the proposed method in the displacement reconstruction of Euler–Bernoulli beams and Kirchhoff plates, without any paired strain–displacement observations. The PI_DeepONet exhibits remarkable precision in the displacement reconstruction, with the reconstructed results achieving a close proximity, surpassing 99%, to the finite element calculations.

Apple Valsa canker caused by Valsa mali is a serious disease in eastern Asia, especially in China. In our previous proteomics study, monensin sensitivity 1 protein in Valsa mali (VmMon1) was identified to be significantly upregulated during V. mali infection. It was reported Mon1 protein formed a heterodimer called MC (Mon1-Ccz1) complex with caffeine, calcium, and zinc sensitivity 1 protein (Ccz1) in yeast. However, Ccz1 had not been identified in plant-pathogenic fungi such as Fusarium graminearum and Magnaporthe oryzae. Here, we identified a Ccz1 ortholog VmCcz1 in V. mali, by using DELTA-BLAST. The interaction of VmMon1 and VmCcz1 were verified using yeast two-hybrid assay, bimolecular fluorescence complementation, and co-immunoprecipitation assays. Further yeast three-hybrid screenings determined that VmRab7 (Ras-related protein in V. mali) interacted with the MC complex. Targeted gene deletion showed that the ∆VmMon1 and ∆VmCcz1 mutants were defective in vegetative growth, conidiation, and pathogenicity. In addition, both mutants were more sensitive to osmotic and oxidative stresses and intracellular protein transport inhibitors. Cytological examination revealed that the ∆VmMon1 and ∆VmCcz1 mutants were impaired in vacuole fusion and autophagy. More importantly, expression of pectinase genes decreased in both mutants compared with those of the wild type during infection. Overall, our study identified Mon1 and Ccz1 genes in V. mali and provided evidence that VmMon1 and VmCcz1 are critical components that modulate vacuole fusion and autophagy, thereby affecting the development, conidiation, and pathogenicity of V. mali. [Graphic: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

COL1A1–PDGFB gene fusion uterine sarcoma is an especially rare malignant mesenchymal tumor that was previously classified as an undifferentiated uterine sarcoma due to the lack of specific features of differentiation. Till now, only five cases have been reported, and here we presented another case recently diagnosed in a Chinese woman who had vaginal bleeding. She presented with a cervical mass at the anterior lip of the cervix invading the vagina and was treated with laparoscopic total hysterectomy plus bilateral salpingo-oophorectomy (TH+BSO) and partial vaginal wall resection with the final pathology of COL1A1–PDGFB fusion uterine sarcoma. Our aim is to emphasize the importance of differential diagnosis of this rare tumor, as early precise diagnosis may allow patients to benefit from the targeted therapy imatinib. This article also serves as further clinical evidence of this disease, serving to increase clinical awareness of this rare sarcoma to avoid misdiagnosis.

A 12-week feeding experiment was conducted to evaluate the effects of replacing fish oil (FO) with beef tallow (BT) on the fatty acid composition of farmed tiger puffer (Takifugu rubripes). Two replacement strategies were used: a standard Graded Dietary Replacement of FO with BT (GDR strategy) and Alternate Feeding between FO- and BT-based Diets (AFD strategy). The positive and negative control diets were formulated with 6% FO (FO-C group) or BT (BT-C group) as the sole added lipid source. In the GDR strategy, three experimental diets were formulated, with 25, 50 and 75% of the added FO in the FO-C diet replaced with BT, named 25BT, 50BT and 75BT, respectively. In the AFD strategy, alternated feeding patterns between the FO-C and BT-C diet—namely, 1, 2 and 3 weeks with BT-C followed by 1 week feeding with FO-C (1BT-1FO, 2BT-1FO and 3BT-1FO, respectively)—were applied. Each diet or feeding strategy was assigned to triplicate tanks. The results showed that dietary BT inclusion reduced the contents of long-chain polyunsaturated fatty acids (LC-PUFA) in both the muscle and liver (edible tissues for this species) of the experimental fish, and the liver displayed a more drastic decrease than the muscle. The LC-PUFA content linearly decreased with the decreasing dietary FO levels in the GDR strategy. However, in the AFD strategy, a linear relationship was not observed between the LC-PUFA content and the FO feeding duration. The 3BT-1FO treatment resulted in higher LC-PUFA content than 2BT-1FO. When comparing the two strategies with the same final FO administration level—namely, 50BT vs. 1BT-1FO, and in particular, 75BT vs. 3BT-1FO—the AFD strategy resulted in higher LC-PUFA contents in both the muscle and liver than the GDR strategy. In conclusion, when FO was replaced with BT in the diets, alternate feeding between FO- and BT-based diets resulted in a higher LC-PUFA content than the standard direct replacement. Three weeks of feeding with BT-C followed by one week of feeding with FO-C appeared to be a good alternate feeding pattern. This study provided a promising strategy of FO-sparing in fish farming when the LC-PUFA contents were maintained as high as possible.

Obesity-induced metabolic syndrome is a rapidly growing conundrum, reaching epidemic proportions globally. Chronic inflammation in obese adipose tissue plays a key role in metabolic syndrome with a series of local and systemic effects such as inflammatory cell infiltration and inflammatory cytokine secretion. Adipose tissue macrophages (ATM), as one of the main regulators in this process, are particularly crucial for pharmacological studies on obesity-related metabolic syndrome. Ponatinib, a multi-targeted tyrosine kinase inhibitor originally used to treat leukemia, has recently been found to improve dyslipidemia and atherosclerosis, suggesting that it may have profound effect on metabolic syndrome, although the mechanisms underlying have not yet been revealed. Here we discovered that ponatinib significantly improved insulin sensitivity in leptin deficient obese mice. In addition to that, ponatinib treatment remarkably ameliorated high fat diet-induced hyperlipidemia and inhibited ectopic lipid deposition in the liver. Interestingly, although ponatinib did not reduce but increase the weight of white adipose tissue (WAT), it remarkably suppressed the inflammatory response in WAT and preserved its function. Mechanistically, we showed that ponatinib had no direct effect on hepatocyte or adipocyte but attenuated free fatty acid (FFA) induced macrophage transformation from pro-inflammatory to anti-inflammatory phenotype. Moreover, adipocytes co-cultured with FFA-treated macrophages exhibited insulin resistance, while pre-treat these macrophages with ponatinib can ameliorate this process. These results suggested that the beneficial effects of ponatinib on metabolic disorders are achieved by inhibiting the inflammatory phenotypic transformation of ATMs, thereby maintaining the physiological function of adipose tissue under excessive obesity. The data here not only revealed the novel therapeutic function of ponatinib, but also provided a theoretical basis for the application of multi-target tyrosine kinase inhibitors in metabolic diseases.

The fatty acid accumulation in fish tissues are closely related to fish sex, yet the sex differences in fish fatty acids have not been fully known. This experiment investigated the sex differences in fatty acid composition of Chinese tongue sole (Cynoglossus semilaevis), which have typical sexual dimorphism and reversal. Three sexes, namely females, males and pseudomales, were involved in this study. Five batches of fish samples were collected from different fish farms in Shandong Province, China. These fish were identified to be at the gonadal development stage of III–IV. The disparity of fatty acid between sexes (female vs male and pseudomale vs. male) was evaluated by the distance coefficient (Dsex) and multi-variate similarity of percentages analysis (SIMPER). The highest Dsex values between females and males were found in gonad, followed by liver and eye. The fatty acids that differed between females and males were mainly DHA, 16:1n-7, 18:1n-9, and 18:0. The sex difference in DHA and 18:1n-9 contributed significantly to the overall sex difference in fatty acid of brain, eye, and gonad, whereas that in 16:1n-7 contributed significantly in heart, gill, liver, and muscle. The sex difference in 18:0 contributed significantly to the overall sex difference in fatty acid of heart, gill, gut, and skin. The sex differences in fatty acid between pseudomales and males were generally insignificant. In conclusion, at this gonadal development stage (III–IV), the sex differences in fatty acid between female and male Chinese tongue sole have emerged, mainly in the gonad. The testes had higher DHA levels but lower levels of 16:1n-7 and 18:1n-9 than ovaries. In addition, for pseudomales, the phenotypic sex more substantially determined the fatty acid composition than the genetic sex.

Abstract Background Monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL) is a rare and aggressive subtype of lymphoma. The most common site of origin is small intestine. Patients are often presented with diagnosis of intestinal perforation with abdominal pain as the main consulting symptoms. Because of the deficiency of specific diagnostic measures and effective management, diagnosis is often confirmed in advanced stage with poor prognosis. Case presentation Here, we introduce a patient who has suffered from abdominal pain and diarrhea, and eventually been diagnosed as Monomorphic epitheliotropic intestinal T-cell lymphomas. Conclusion MEITL is rare in clinical practice with deficiency of early diagnostic measures and poor prognosis. Therefore, any patient with ambiguous gastrointestinal symptoms or perforation of the digestive tract where the primary lesion is difficult to identify should be alert to the possibility of this disease.

Photocatalysis is a potential strategy to solve energy and environmental problems. The development of new sustainable photocatalysts is a current topic in the field of photocatalysis. ZnIn2S4, a visible light-responsive photocatalyst, has attracted extensive research interest in recent years. Due to its suitable band gap, strong chemical stability, durability, and easy synthesis, it is expected to become a new hot spot in the field of photocatalysis in the near future. This mini-review presents a comprehensive summary of the modulation strategies to effectively improve the photocatalytic activity of ZnIn2S4 such as morphology and structural engineering, defects engineering, doping engineering, and heterojunction engineering. This review aims to provide reference to the proof-of-concept design of highly active ZnIn2S4-based photocatalysts for the enhanced hydrogen evolution reaction.

Abstract Background N6-methyladenosine (m6A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain. Results We show that m6A modification displays temporal and spatial dynamics during neurodevelopment and aging. Genes that are temporally differentially methylated are more prone to have mRNA expression changes and affect many pathways associated with nervous system development. Furthermore, m6A shows a distinct tissue-specific methylation profile, which is most pronounced in the hypothalamus. Tissue-specific methylation is associated with an increase in mRNA expression and is associated with tissue-specific developmental processes. During the aging process, we observe significantly more m6A sites as age increases, in both mouse and human. We show a high level of overlap between mouse and human; however, humans at both young and old ages consistently show more m6A sites compared to mice. Differential m6A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m6A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m6A methylation in a mouse model of Alzheimer’s disease, which is correlated with reduced protein levels. Conclusions Our results suggest that m6A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m6A controls protein levels of key genes involved in Alzheimer’s disease-associated pathways, suggesting that m6A plays an important role in aging and neurodegenerative disease.

Booming fish farming results in relative shortage of fish oil (FO), making it urgent to explore alternative lipid sources. This study comprehensively investigated the efficacy of FO replacement with poultry oil (PO) in diets of tiger puffer (average initial body weight, 12.28 g). An 8-week feeding trial was conducted with experimental diets, in which graded levels (0, 25, 50, 75, and 100%, named FO-C, 25PO, 50PO, 75PO, and 100PO, respectively) of FO were replaced with PO. The feeding trial was conducted in a flow-through seawater system. Each diet was fed to triplicate tanks. The results showed that FO replacement with PO did not significantly affect the growth performance of tiger puffer. FO replacement with PO at 50-100% even slightly increased the growth. PO feeding also had marginal effects on fish body composition, except that it increased the liver moisture content. Dietary PO tended to decrease the serum cholesterol and malondialdehyde content but increase the bile acid content. Increasing levels of dietary PO linearly upregulated the hepatic mRNA expression of the cholesterol biosynthesis enzyme, 3-hydroxy-3-methylglutaryl-CoA reductase, whereas high levels of dietary PO significantly upregulated the expression of the critical regulatory enzyme of bile acid biosynthesis, cholesterol 7-alpha-hydroxylase. In conclusion, poultry oil is a good substitution for fish oil in the diets of tiger puffer. Poultry oil could replace 100% added fish oil in the diet of tiger puffer, without adverse effects on growth and body composition.

Booming fish farming results in a relative shortage of fish oil (FO) supply, meaning that alternative oils are increasingly used in fish feeds, which leads to reduction of long-chain polyunsaturated fatty acids (LC-PUFAs) and other relevant changes in fish products. This study investigated the efficacy of an FO-finishing strategy in recovering the muscle quality of farmed tiger puffer. An eight-week feeding trial (growing-out period) was conducted with five experimental diets, in which graded levels (0 (control), 25, 50, 75, and 100%) of added FO were replaced by poultry oil (PO). Following the growing-out period was a four-week FO-finishing period, during which fish in all groups were fed the control diet. Dietary PO significantly decreased the muscle LC-PUFA content, whereas in general, the FO-finishing strategy recovered it to a level comparable with that of the group fed FO continuously. The recovery efficiency of EPA was higher than that of DHA. Dietary PO also led to changes of volatile flavor compounds in the muscle, such as butanol, pentenal, and hexenal, whereas the FO-finishing strategy mitigated the changes. In conclusion, the FO-finishing strategy is promising in recovering the LC-PUFA and volatile-flavor-compound composition in farmed tiger puffer after the feeding of PO-based diets.

Concerning the biomechanics and energy consumption of the lower limbs, a soft exoskeleton for the powered plantar flexion of the ankle, named A-Suit, was developed to improve walking endurance in the lower limbs and reduce metabolic consumption. The method of ergonomics design was used based on the biological structures of the lower limbs. A profile of auxiliary forces was constructed according to the biological force of the Achilles tendon, and an iterative learning control was applied to shadow this auxiliary profile by iteratively modifying the traction displacements of drive units. During the evaluation of the performance experiments, four subjects wore the A-Suit and walked on a treadmill at different speeds and over different inclines. Average heart rate was taken as the evaluation index of metabolic consumption. When subjects walked at a moderate speed of 1.25 m/s, the average heart rate Hav under the Power-ON condition was 7.25 ± 1.32% (mean ± SEM) and 14.40 ± 2.63% less than the condition of No-suit and Power-OFF. Meanwhile, the additional mass of A-Suit led to a maximum Hav increase of 7.83 ± 1.44%. The overall reduction in Hav with Power-ON over the different inclines was 6.93 ± 1.84% and 13.4 ± 1.93% compared with that of the No-Suit and Power-OFF condition. This analysis offers interesting insights into the viability of using this technology for human augmentation and assistance for medical and other purposes.

Summary: Transcriptional silencing of the FMR1 gene in fragile X syndrome (FXS) leads to the loss of the RNA-binding protein FMRP. In addition to regulating mRNA translation and protein synthesis, emerging evidence suggests that FMRP acts to coordinate proliferation and differentiation during early neural development. However, whether loss of FMRP-mediated translational control is related to impaired cell fate specification in the developing human brain remains unknown. Here, we use human patient induced pluripotent stem cell (iPSC)-derived neural progenitor cells and organoids to model neurogenesis in FXS. We developed a high-throughput, in vitro assay that allows for the simultaneous quantification of protein synthesis and proliferation within defined neural subpopulations. We demonstrate that abnormal protein synthesis in FXS is coupled to altered cellular decisions to favor proliferative over neurogenic cell fates during early development. Furthermore, pharmacologic inhibition of elevated phosphoinositide 3-kinase (PI3K) signaling corrects both excess protein synthesis and cell proliferation in a subset of patient neural cells.

Extracellular polymeric substances (EPS) are extracellular metabolites of microorganisms, highly associated with microbial function, adaptation, and growth. The main compounds in EPS have been revealed to be proteins, polysaccharides, nucleic acids, humic substances, lipids, etc. EPS are not only biomass, but also a biogenic material. EPS have high specific surface, abundant functional groups, and excellent degradability. In addition, they are more extensible to the environment than the microbial cells themselves, which exhibits their huge advantages. Therefore, they have been applied in many fields, such as the environment, ecosystem, basic commodities, and medicine. However, the functions of EPS highly depend on the suitable extraction process, as different extraction methods have different effects on their composition, structure, and function. There are many types of EPS extraction methods, in which physical and chemical methods have been widely utilized. This review summarizes the extraction methods and applications of EPS. In addition, it considers some important gaps in current knowledge, and indicates perspectives of EPS for their future study. [ABSTRACT FROM AUTHOR]