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BackgroundResearch of immunotherapy for cholangiocarcinoma has yielded some results, but more clinical data are needed to prove its efficacy and safety. Moreover, there is a need to identify accessible indexes for selecting patients who may benefit from such treatments.MethodsThe medical records of 66 cholangiocarcinoma patients who underwent immunotherapy were retrospectively collected. The effectiveness of immunotherapy was assessed by tumor response, progression-free survival (PFS), and overall survival (OS), while safety was evaluated by adverse events during treatment. Univariate and multivariate Cox regression analyses were performed to identify prognostic risk factors for PFS and OS, and Kaplan-Meier curves of potential prognostic factors were drawn.ResultsOverall, in this study, immunotherapy achieved an objective response rate of 24.2% and a disease control rate of 89.4% for the included patients. The median PFS was 445 days, and the median OS was 772.5 days. Of the 66 patients, 65 experienced adverse events during treatment, but none had severe consequences. Multivariate Cox analysis indicated that tumor number is a prognostic risk factor for disease progression following immunotherapy in cholangiocarcinoma patients, while tumor differentiation and the fibrosis-4 (FIB-4) index are independent risk factors for OS.ConclusionIn general, immunotherapy for cholangiocarcinoma is safe, with adverse events remaining within manageable limits, and it can effectively control disease progression in most patients. The FIB-4 index may reflect the potential benefit of immunotherapy for patients with cholangiocarcinoma.

Hepatoid carcinoma is an extrahepatic primary tumor displaying characteristics reminiscent of hepatocellular carcinoma differentiation, which is found in various organs, such as the stomach, ovaries, gallbladder, and pancreas. Reports of pancreatic hepatoid carcinoma remain scarce. Consequently, understanding of this disease remains a priority, with no established consensus on its diagnosis and management. Here, we reported the case of a 45-year-old woman diagnosed with hepatoid carcinoma located in the pancreatic head, accompanied by multiple lymph node metastases. Following pancreaticoduodenectomy, the patient developed liver metastases within 3 months. Subsequently, she underwent adjuvant therapy consisting of Teysuno and Durvalumab following microwave ablation for the liver metastases. Remarkably, the patient has survived for one year without significant disease progression. This case underscores the potential efficacy of immunotherapy as a promising treatment option for pancreatic hepatoid carcinoma. Further research and clinical trials are warranted to explore the optimal management strategies for this rare and challenging malignancy.

Abstract Background Benefiting from increased life expectancy and improved perioperative management, more elderly patients with pancreatic head cancer (PHC) underwent pancreaticoduodenectomy (PD). However, individualized predictive models for the safety and efficacy of PD is still lacking. this study aimed to developed three safety‐ and efficacy‐related risk calculators for elderly (> = 65 years) PHC patients. Methods This study was designed with two research cohorts, namely, the training cohort and the validation cohort, and comprises four general steps: (1) Risk factors were analyzed for the incidence of postoperative complications, cancer‐specific survival (CSS), and overall survival (OS) in the training cohort (N = 271) using logistic and Cox‐regression analysis. (2) Nomograms were then plotted based on the above results. (3) The accuracy of the developed nomogram models was then verified with the validation cohort (N = 134) data using consistency index (C‐index) and calibration curves. (4) We then evaluated the efficacy of these nomograms using decision curve analysis (DCA) in both the training and validation cohorts, and ultimately constructed three online calculators based on these nomograms. Results We identified ASA, diabetes, smoking, and lymph node invasion as predisposing risk factors for postoperative complications, and the predictive factors that affected both OS and CSS were ASA, diabetes, BMI, CA19‐9 level, and tumor diameter. By integrating the above risk factors, we constructed three nomograms on postoperative complication, CSS, and OS. The C‐index for complication, CSS, and OS were 0.824, 0.784, and 0.801 in the training cohort and 0.746, 0.718, and 0.708 in the validation cohort. Moreover, the validation curves and DCA demonstrated good calibration and robust compliance in both training and validation cohorts. We then developed three web calculators (https://caiming.shinyapps.io/CMCD/, https://caiming.shinyapps.io/CMCSS/, and https://caiming.shinyapps.io/CMOS/) to facilitate the use of the nomograms. Conclusions The calculators demonstrated promising performance as an tool for predicting the safety and efficacy of PD in elderly PHC patients.

Abstract Objective Clinical practitioners face a significant challenge in maintaining a healthy balance between overtreatment and missed diagnosis in the management of intraductal papillary mucinous neoplasm (IPMN). The current study aimed to identify significant risk factors of malignant IPMN from a series of clinical and radiological parameters that are widely available and noninvasive and develop a method to individually predict the risk of malignant IPMN to improve its management. Methods We retrospectively investigated 168 patients who were pathologically diagnosed with IPMN after individualized pancreatic resection between June, 2012 and December, 2020. Independent predictors determined using both univariate and multivariate analyses to construct a predictive model. The discriminatory power of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC). Decision curve analysis was performed to demonstrate the clinical usefulness of the nomogram. Internal cross validation was performed to assess the validity of the predictive model. Results In the multivariate analysis, five significant independent risk factors were identified: increased serum CA19‐9 level, low prognostic nutritional index (PNI), cyst size, enhancing mural nodule, and main pancreatic duct diameter. The nomogram based on the parameters mentioned above had outstanding performance in distinguishing malignancy, with an AUC of 0.907 (95% confidence interval: 0.859–0.956, p

Abstract Background We have limited information about neuroendocrine carcinoma (NEC) of the gallbladder. The purpose of this paper is to compare clinical and pathological features between different age groups and prognostic factors for gallbladder NEC and how it differs from adenocarcinoma (ADC) of the gallbladder. Patients and methods This study included 28 gallbladder NEC patients and 137 ADC patients whose clinical characteristics and pathological findings were retrospectively collected. Propensity score matching and Cox regression analysis were used for the analysis of prognostic factors. Results We divided NEC patients into two groups based on the age more than or less than 60 years. Most of the NEC patients less than 60 years old complained of abdominal pain or discomfort (p = 0.038), and more younger patients accepted adjuvant therapy (p = 0.020) than older patients did. CD56 was positive in all patients more than 60 years old, which is significantly higher than that of younger patients (p = 0.039). The mean age was similar between NEC and ADC patients. After eliminating confounding factors between NEC and ADC patients, the overall survival rates were still lower in NEC patients. Univariate analysis extracted six possible risk factors. Multivariate analysis indicated that surgery type, tumor size, and existence of gallstones were independent prognostic factors. Conclusion The overall survival of gallbladder NEC is not associated with age. In this study, surgical method and tumor size were found to be independent risk factors for NECs. In addition, NEC patients have a worse prognosis than ADC patients with similar clinical and pathological features.

Abstract Background Pancreatic ductal adenocarcinoma is one of the most aggressive cancers, with a 5-year survival rate of less than 8%. The complicated tumor microenvironment, particularly TGF-β, provides possible convenience for the progression of PC cells. TGF-β regulates critical cellular processes, including autophagy. However, the mechanism and effects of TGF-β-mediated autophagy are still poorly understood. Methods Bioinformatics analysis, western blot, transmission electron microscopy and confocal microscopy were used to identify that TFEB is the key factors in TGF-β-induced autophagy. The biological effects of TFEB-driven autophagy were investigated in vitro using transwell and wound healing assays and in vivo using liver metastasis and LSL-KrasG12D/Pdx1-Cre mice models. Luciferase assays and motif analysis were used to assess regulation of RAB5A gene promoter activity by TGF-β-induced TFEB. TFEB levels were measured by real-time PCR, western blot and immunohistochemical staining in clinical pancreatic ductal adenocarcinoma tissues. Results We demonstrated that TGF-β induces TFEB expression via the canonical smad pathway in Smad4-positive PC cells and facilitates TFEB-mediated autophagic activation. TFEB-driven autophagy caused by TGF-β regulates RAB5A-dependent endocytosis of Itgα5 and promotes progression of PC cells. We further showed that enhanced TFEB expression and its direct target RAB5A both predict poor prognosis in PC patients. Conclusions Our findings reveal TFEB-driven autophagy is required for TGF-β induced migration and metastasis of PC cells by promoting endocytosis of Itgα5β1 and focal adhesion disassembly through the TGF-β-TFEB-RAB5A axis. Our results highlight the potential utility of suppressing TFEB-driven autophagy to block PC metastasis.

A new scheme for accelerating positively charged particles in a plasma-wakefield accelerator is proposed. If the proton drive beam propagates in a hollow plasma channel, and the beam radius is of order of the channel width, the space charge force of the driver causes charge separation at the channel wall, which helps to focus the positively charged witness bunch propagating along the beam axis. In the channel, the acceleration buckets for positively charged particles are much larger than in the blowout regime of the uniform plasma, and stable acceleration over long distances is possible. In addition, phasing of the witness with respect to the wave can be tuned by changing the radius of the channel to ensure the acceleration is optimal. Two-dimensional simulations suggest that, for proton drivers likely available in future, positively charged particles can be stably accelerated over 1 km with the average acceleration gradient of 1.3 GeV/m.

In plasma-based accelerators, electrons are accelerated by ultrahigh gradient of 1–100 GV/m and undergo the focusing force with the same order as the accelerating force. Heated electrons are injected in a plasma wake and exhibit the betatron oscillation that generates synchrotron radiation. Intense betatron radiation from laser-plasma accelerators is attractive x-ray/gamma-ray sources, while it produces radiation loss and significant effects on energy spread and transverse emittance via the radiation reaction force. In this article, electron beam dynamics on transverse emittance and energy spread with considering radiation reaction effects are studied numerically. It is found that the emittance growth and the energy spread damping initially dominate and balance with radiative damping due to the betatron radiation. Afterward the emittance turns to decrease at a constant rate and leads to the equilibrium at a nanometer radian level with growth due to Coulomb scattering at PeV-level energies. A constant radiation loss rate R_{T}=2/3 is found without regard to the electron beam and plasma conditions. Self-cooling of electron beams due to betatron radiation may guarantee TeV-range linear colliders and give hints on astrophysical ultrahigh-energy phenomena.

Abstract Trimethylamine-n-oxide (TMAO) is a metabolite of intestinal flora following the consumption of phosphatidylcholine-rich foods. Clinical cohort studies have shown that plasma TMAO may be a risk factor for cancer development, including hepatocellular carcinoma (HCC), but fundamental research data supporting this hypothesis are lacking. In this study, HCC cells were treated with TMAO in vivo and in vitro to evaluate the effect on some indicators related to the malignancy degree of HCC, and the relevant molecular mechanisms were explored. In vitro, TMAO promoted the proliferation and migration of HCC cells and significantly upregulated the expression of proteins related to epithelial–mesenchymal transformation (EMT). In vivo, after HCC cells were inoculated subcutaneously in nude mice given water containing TMAO, the tumors grew faster and larger than those in the mice given ordinary water. The immunohistochemistry analysis showed that proliferation, migration and EMT-related proteins in the tumor tissues were significantly upregulated by TMAO. Furthermore, TMAO obviously enhanced the phosphorylation of MAPK signaling molecules in vivo and in vitro. In conclusion, TMAO promotes the proliferation, migration and EMT of HCC cells by activating the MAPK pathway.

Abstract Patulin (PAT) is a common mycotoxin in moldy fruits that causes gastrointestinal injury if accidentally ingested. Some studies have reported the symptoms of intestinal injury caused by PAT. However, the effects of PAT on the gut microbiota and gut metabolism remain to be investigated, which is important for clarifying the toxicological mechanisms. Thus, C57/BL6J mice were gavaged once with 0, 1, 4, and 16 mg/kg body weight PAT, and the small intestinal and colonic contents were collected. The 16S rRNA sequencing and targeted and untargeted metabolomics were applied to assess the alterations in microbiota and metabolism, respectively. The results showed that Mycoplasma, Dubosiella, and Enterorhabdus were jointly affected by acute PAT exposure in the small intestinal and colonic contents. Some inflammation‐related bacteria, such as Mycoplasma in the small intestine and Mycoplasma, Alistipes, Eubacterium_coprostanoligenes_group, and Candidatus_saccharimona in the colon, increased with increasing doses of PAT. In metabolic results, amino acids decreased and bile acids elevated in both intestinal contents; lipids increased in the small intestinal contents but decreased in the colonic contents. PAT mainly affected host amino acid and lipid metabolism; it also downregulated microbial tryptophan metabolism and short‐chain fatty acid levels (mainly in the colon), which could be explained by the decrease of Bacteroides and Lactobacillus. These influences in microbial abundances and metabolic levels persisted after PAT and its products were cleared. These results fill a gap in the effects of PAT on the gut microbiota and provide a theoretical basis for elucidating the toxic mechanism of mycotoxins.

Mycotoxin contamination has become a major food safety issue and greatly threatens human and animal health. Patulin (PAT), a common mycotoxin in the environment, is exposed through the food chain and damages the gastrointestinal tract. However, its mechanism of enterotoxicity at the genetic and metabolic levels remains to be elucidated. Herein, the intestinal histopathological and biochemical indices, transcriptome, and metabolome of C57BL/6 J mice exposed to different doses of PAT were successively assessed, as well as the toxicokinetics of PAT in vivo. The results showed that acute PAT exposure induced damaged villi and crypts, reduced mucus secretion, decreased SOD and GSH-Px activities, and enhanced MPO activity in the small intestine and mild damage in the colon. At the transcriptional level, the genes affected by PAT were dose-dependently altered in the small intestine and fluctuated in the colon. PAT primarily affected inflammation-related signaling pathways and oxidative phosphorylation in the small intestine and immune responses in the colon. At the metabolic level, amino acids decreased, and extensive lipids accumulated in the small intestine and colon. Seven metabolic pathways were jointly affected by PAT in two intestinal sites. Moreover, changes in PAT products and GST activity were detected in the small intestinal tissue but not in the colonic tissue, explaining the different damage degrees of the two sites. Finally, the integrated results collectively explained the toxicological mechanism of PAT, which damaged the small intestine directly and the colon indirectly. These results paint a clear panorama of intestinal changes after PAT exposure and provide valuable information on the exposure risk and toxic mechanism of PAT.

Abstract Agaric is a dual‐purpose fungus for medicine and food, which is considered a healthcare product. However, in cultivation and production, agaric is contaminated by a variety of molds, resulting in a decline in quality and yield. Fusarium, as one of the poisonous filamentous fungi, seriously threatens the healthy development of the agaric industry and even affects human health. Therefore, it is necessary to establish timely and accurate identification and rapid detection of pathogens and crops. In this study, the visible near infrared hyperspectral imaging was used to obtain the image and spectral information, and the best classification model was selected and established to quickly distinguish Fusarium oxysporum from Fusarium verticillioides, which was also successfully applied for the preliminary identification of agaric infection. This approach could provide a nondestructive manner for rapid identification and detection of pathogenic fungi contamination in agaric.

Abstract Akebia fruit is a plant used for both medicinal and edible purposes. In recent years, due to the rich phytochemical composition with bioactive effects, Akebia fruit has attracted increasing attention on its composition analysis, active ingredients identification, and product applications. For example, the protein, sugar, amino acids, and vitamin C content of the pulp is higher than that of ordinary fruit. The seeds are not only processed into edible oil, it is also rich in protein and have the potential to be developed into a new resource with beneficial effects on human health. However, the research on the understanding of Akebia as a plant fruit is relatively lacking. In this review, an overview of Akebia fruit from food perspectives, including extraction methods and phytochemicals, bioactive functions, and various applications, were summarized. Finally, based on the current status and existing challenges, the prospect and future development direction of Akebia fruit were discussed.

Abstract Ethyl carbamate (EC) is a kind of genotoxic and carcinogenic substance and potentially harmful to human health. In this study, simple and effective removal of EC from liquor samples by using the magnetic mesoporous adsorbent (Fe3O4@COFs) was investigated. Gas chromatography and triple quadrupole tandem mass spectrometry (GC‐MS/MS) was used to monitor the whole of adsorption process. The results showed that the adsorbent has high efficiency and fast adsorption capacity. Under the optimized adsorption parameters, pseudo‐first‐order and pseudo‐second‐order kinetic models were employed to reveal the underlying sorption mechanism. Results indicated that the adsorption of EC on Fe3O4@COFs is more consistent with the pseudo‐second‐order model. Furthermore, an effective method for the adsorption and detection of EC was successfully developed, which exhibited good linearity with R2 ranging from 0.9954 to 0.9998, satisfactory recoveries in the range of 86.9%–116.2%, and the relative standard deviations (RSD) was lower than 5.8%. Fe3O4@COFs showed good stability and excellent performance in removing EC from liquor samples. It is expected that the proposed magnetic COFs hold great promise for liquor sample pretreatment and be extended for application in other fields.

Abstract The interplay between hepatocellular carcinoma (HCC) cells and the tumor microenvironment is essential for hepatocarcinogenesis, but their contributions to HCC development are incompletely understood. We assessed the role of ANGPTL8, a protein secreted by HCC cells, in hepatocarcinogenesis and the mechanisms through which ANGPTL8 mediates crosstalk between HCC cells and tumor-associated macrophages. Immunohistochemical, Western blotting, RNA-Seq, and flow cytometry analyses of ANGPTL8 were performed. A series of in vitro and in vivo experiments were conducted to reveal the role of ANGPTL8 in the progression of HCC. ANGPTL8 expression was positively correlated with tumor malignancy in HCC, and high ANGPTL8 expression was associated with poor overall survival (OS) and disease-free survival (DFS). ANGPTL8 promoted HCC cell proliferation in vitro and in vivo, and ANGPTL8 KO inhibited the development of HCC in both DEN-induced and DEN-plus-CCL4-induced mouse HCC tumors. Mechanistically, the ANGPTL8–LILRB2/PIRB interaction promoted polarization of macrophages to the immunosuppressive M2 phenotype in macrophages and recruited immunosuppressive T cells. In hepatocytes, ANGPTL8-mediated stimulation of LILRB2/PIRB regulated the ROS/ERK pathway and upregulated autophagy, leading to the proliferation of HCC cells. Our data support the notion that ANGPTL8 has a dual role in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis.

Introduction: High calorie intake is known to induce nonalcoholic fatty liver disease (NAFLD) by promoting chronic inflammation. However, the mechanisms are poorly understood. Objectives: This study examined the roles of ANGPTL8 in the regulation of NAFLD-associated liver fibrosis progression induced by high fat diet (HFD)-mediated inflammation. Methods: The ANGPTL8 concentration was measured in serum samples from liver cancer and liver cirrhosis patients. ANGPTL8 knockout(KO) mice were used to induce disease models (HFD, HFHC and CCL4) followed by pathological staining, western blot and immunohistochemistry. Hydrodynamic injection of an adeno-associated virus 8 (AAV8) was used to establish a model for restoring ANGPTL8 expression specifically in ANGPTL8 KO mice livers. RNA-sequencing, protein array, Co-IP, etc. were used to study ANGPTL8′s mechanisms in regulating liver fibrosis progression, and drug screening was used to identify an effective inhibitor of ANGPTL8 expression. Results: ANGPTL8 level is associated with liver fibrogenesis in both cirrhosis and hepatocellular carcinoma patients. Mouse studies demonstrated that ANGPTL8 deficiency suppresses HFD-stimulated inflammatory activity, hepatic steatosis and liver fibrosis. The AAV-mediated restoration of liver ANGPTL8 expression indicated that liver-derived ANGPTL8 accelerates HFD-induced liver fibrosis. Liver-derived ANGPTL8, as a proinflammatory factor, activates HSCs (hepatic stellate cells) by interacting with the LILRB2 receptor to induce ERK signaling and increase the expression of genes that promote liver fibrosis. The FDA-approved anti-diabetic drug metformin, an ANGPTL8 inhibitor, inhibited HFD-induced liver fibrosis in vivo. Conclusions: Our data support that ANGPTL8 is a proinflammatory factor that accelerates NAFLD-associated liver fibrosis induced by HFD. The serum ANGPTL8 level may be a potential and specific diagnostic marker for liver fibrosis, and targeting ANGPTL8 holds great promise for developing innovative therapies to treat NAFLD-associated liver fibrosis.

Summary: The recovery of spent lithium-ion batteries has not only economic value but also ecological benefits. In this paper, molten-salt electrolysis was employed to recover spent LiCoO2 batteries, in which NaCl-Na2CO3 melts were used as the electrolyte, the graphite rod and the mixtures of the spent LiCoO2 cathode and anode were used as the anode and cathode, respectively. During the electrolysis, the LiCoO2 was electrochemically reduced to Co, and Li+ and O2− entered into the molten salt. The O2− was discharged at the anode to generate CO2 and formed Li2CO3. After electrolysis, the cathodic products were separated by magnetic separation to obtain Co and graphite, and Li2CO3 was recovered by water leaching. The recovery efficiencies of Li, Co, and graphite reached 99.3%, 98.1%, and 83.6%, respectively. Overall, this paper provides a simple and efficient electrochemical method for the simultaneous recovery of the cathode and the anode of spent LiCoO2 batteries.

Abstract Alicyclobacillus acidoterrestris (A. acidoterrestris), a kind of spore‐forming bacterium, could causes spoilage of fruit juices, which results in pecuniary losses to the industry. Unfortunately, the conventional methods used to identify this bacterium are laborious and complex. In this work, copper‐based metal‐organic frameworks (Cu‐MOFs) with intrinsic peroxidase‐like activity were fabricated by a self‐assembly method. Based on the properties of Cu‐MOFs, a colorimetric assay was developed for the detection of guaiacol, a characteristic metabolite of A. acidoterrestris and chromogenic substrate of peroxidase. Under optimal conditions, an excellent linear relationship was achieved over a range of guaiacol (0.01–0.4 mM), with a limit of detection (LOD) as low as 0.003 mM. This biosensor also showed a satisfactory sensing performance towards guaiacol, allowing the identification of A. acidoterrestris with high selectivity in a real sample. This present study provides a new perspective for the exploration of more sensitive and convenient methods for A. acidoterrestris detection.

Abstract Doxorubicin (DOX) is a commonly used antitumor drug, but its application has been limited because of its strong cardiac damage. This study aims to explore the role of NSUN2 in DOX-induced heart injury. C57BL/6J mice were intraperitoneally injected with 20 mg/Kg DOX to induce heart injury. After 3 days, the cardiac function, cardiac histopathology, myocardial apoptosis, and the expression level of NSUN2 were detected. In vitro, H9C2 cells were transfected with NSUN2 siRNA or overexpressed lentivirus and then treated with 500 ng/ml DOX. After 24 h, the changes in reactive oxygen species (ROS), apoptosis, and NSUN2 expression were detected. After DOX treatment, both in vitro and in vivo experiments showed that the cardiac function decreased, the number of apoptotic cells increased, and the expression level of NSUN2 increased. Interfering the expression of NSUN2 by siRNA promoted DOX-induced heart injury, while overexpression of NSUN2 could inhibit DOX-induced heart injury. Further study showed that NSUN2 promoted antioxidative stress by upregulating the Nrf2 protein level. In addition, NSUN2 overexpression could increase the half-life of Nrf2 mRNA. m5C RNA methylation immunoprecipitation (MeRIP) also showed that the level of Nrf2 m5C mRNA was significantly increased in NSUN2 overexpressed group when compared to the GFP group. NSUN2 enhances the expression of Nrf2 by promoting Nrf2 mRNA m5C modification and enhances its antioxidative stress effect to alleviate DOX-induced myocardial injury.

The study explored the potential protective impact of the probiotic fungus Eurotium amstelodami in Fuzhuan brick tea on ulcerative colitis, along with the underlying mechanism. A spore suspension of E. amstelodami was administered to C57BL/6 mice to alleviate DSS-induced colitis. The findings indicated that administering E. amstelodami evidently enhanced the ultrastructure of colonic epithelium, showing characteristics such as enhanced TJ length, reduced microvilli damage, and enlarged intercellular space. After HLL supplementation, the activation of the liver inflammation pathway, including TLR4/NF-kB and NLRP3 inflammasome caused by DSS, was significantly suppressed, and bile acid metabolism, linking liver and gut, was enhanced, manifested by restoration of bile acid receptor (FXR, TGR5) level. The dysbiosis of the gut microbes in colitis mice was also restored by HLL intervention, characterized by the enrichment of beneficial bacteria (Lactobacillus, Bifidobacterium, Akkermansia, and Faecalibaculum) and fungi (Aspergillus, Trichoderma, Wallemia, Eurotium, and Cladosporium), which was closely associated with lipid metabolism and amino acid metabolism, and was negatively correlated with inflammatory gene expression. Hence, the recovery of gut microbial community structure, implicated deeply in the inflammatory index and metabolites profile, might play a crucial role in the therapeutic mechanism of HLL on colitis.

Introduction Pancreatoduodenectomy (PD) is one of the most complex abdominal operations to perform, and it is usually conducted for tumours of the periampullary region and chronic pancreatitis. Minimally invasive surgery has been progressively being developed for pancreatic surgery, first with the advent of hybrid-laparoscopy and recently with total laparoscopic surgery. Issues including the safety and efficacy of total laparoscopic pancreaticoduodenectomy (TLPD) and open pancreaticoduodenectomy (OPD) are currently being debated. Studies comparing these two surgical techniques are emerging, and large randomised controlled trials (RCTs) are lacking but are clearly required.Methods and analysis TJDBPS01 is a multicentre, prospective, randomised controlled, parallel-group, superiority trial in 14 centres with pancreatic surgery experts who have performed ≥104 TLPDs and OPDs. A total of 656 patients who will undergo PD are randomly allocated to the TLPD group or OPD group in a 1:1 ratio. The trial hypothesis is that TLPD has superior or equivalent safety and advantages in postoperative recovery compared with OPD. The primary outcome is the postoperative length of stay.Ethics and dissemination The Instituitional Review Board Approval of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology has approved this trial and will be routinely monitoring the trial at frequent intervals, as will an independent third-party organisation. Any results from this trial (publications, conference presentations) will be published in peer-reviewed journals and conference proceedings. [ABSTRACT FROM AUTHOR]

Abstract Mycotoxins are the secondary metabolites of fungi in food and can be toxic to people. Therefore, developing simple, sensitive, and specific detection methods to detect mycotoxins in food is essential for ensuring food safety. Fluorescent aptasensors for the detection of mycotoxins in food have developed rapidly. They are simple and fast with high affinity and specificity. However, fluorescent aptasensors have not yet been applied in officially approved standards so far. This review elucidates fluorescent aptasensors for mycotoxin detection, including principles, constituted elements, types, and applications. Screening results of aptamers and each aptamer sequence used in fluorescent aptasensors are summarized to facilitate further research for later studies. We also focused on fluorescent probes, nanomaterials, and other strategies in the process of constructing fluorescent aptasensors. We then discuss current challenges and future perspectives in fluorescent aptasensors for mycotoxin detection.

Burkholderia gladioli pv. cocovenenans is a serious safety issue in black fungus due to the deadly toxin, bongkrekic acid. This has triggered the demand for an efficient toxigenic phenotype recognition method. The objective of this study is to develop an efficient method for the recognition of toxin-producing B. gladioli strains. The potential of multilocus sequence typing and a back propagation neural network for the recognition of toxigenic B. cocovenenans was explored for the first time. The virulent strains were isolated from a black fungus cultivation environment in Qinba Mountain area, Shaanxi, China. A comprehensive evaluation of toxigenic capability of 26 isolates were conducted using Ultra Performance Liquid Chromatography for determination of bongkrekic acid and toxoflavin production in different culturing conditions and foods. The isolates produced bongkrekic acid in the range of 0.05–6.24 mg/L in black fungus and a highly toxin-producing strain generated 201.86 mg/L bongkrekic acid and 45.26 mg/L toxoflavin in co-cultivation with Rhizopus oryzae on PDA medium. Multilocus sequence typing phylogeny (MLST) analysis showed that housekeeping gene sequences have a certain relationship with a strain toxigenic phenotype. We developed a well-trained, back-propagation neutral network for prediction of toxigenic phenotype in B. gladioli based on MLST sequences with an accuracy of 100% in the training set and an accuracy of 86.7% in external test set strains. The BP neutral network offers a highly efficient approach to predict toxigenic phenotype of strains and contributes to hazard detection and safety surveillance.

Considerable progress has been achieved in the bioaccumulation and transformation of selenium (Se)-enriched lactic acid bacteria (LAB). However, research on the effects of Se on the structure and probiotic potential of LAB is relatively limited. In this study, six industrial LAB strains, including Lactobacillus plantarum 21,805, Lactobacillus paracasei 20,241, Lactobacillus fermentum 21,828, Lactobacillus casei 23,185, Lactobacillus acidophilus 6064, and Lactobacillus plantarum 6076, were cultured in De Man, Rogosa, and Sharpe (MRS) medium containing Se for three generations. High-Se LAB was screened based on bacterial biomass, viable bacterial count, and Se content. Their structural characteristics were analyzed using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The results indicated that LAB growth was influenced by the Se environment, with high Se (20 μg/mL) inhibiting it. At a Se concentration of 10 μg/mL, LAB maintained integrity and exhibited a high Se enrichment ability, with a Se enrichment of 4.88 ± 0.39 mg/g. The intracellular Se existed in an amorphous or non-crystalline form. Furthermore, Se-enriched LAB exhibited enhanced probiotic properties, including tolerance to simulated gastrointestinal fluids, acid resistance, bile salt resistance, and hydrophobicity. Therefore, Se-enriched LAB are expected to develop new functional foods or dietary supplements for human and animal consumption.

Several of the fungal species associated with Fuzhuan brick tea (FBT) are considered as potential probiotics, but few studies have investigated the probiotic properties of these fungi. Here, we isolated 18 fungal strains from two types of FBT and identified these strains based on internal transcribed spacer (ITS) fragment sequence similarity to reference strains (sequence similarity > 98%). Of the 18 strains, 10 tolerated simulated human digestive conditions for sufficient periods in vitro: pH 2-3, 0.3%-0.5% (m/V) bile salts, and artificial gastrointestinal juices. We then measured the antimicrobial activity of the remaining 10 strains against 5 enteropathogenic bacteria and tested the bacteriostatic effects of the thalli and fermentation broth extracts. Of the 6 strains with strong bacteriostatic effects, we eliminated Eurotium cristatum S-9 due to its low hydrophobicity of (26.12 ± 0.35)%. Finally, 2 exhibited good adhesion abilities to human cells (> 100%). Notably, 2 strains can survive in vivo, because they can be isolated from C57BL/6 mice feces. Thus, 2 strains, Aspergillus cristatus H-1 and A. cristatus H-5, are herein identified as promising candidate probiotic strains. It may be put forward a novel research focus on evaluating potential probiotic fungi from FBT.

This study aimed to evaluate the application of encapsulated L. plantarum and eugenol as potential biocontrol agents in sliced apples. The combined encapsulated L. plantarum and eugenol treatment was more effective than separate encapsulated L. plantarum and eugenol treatments, with regards to browning inhibition and consumers panel test. The application of encapsulated L. plantarum and eugenol reduced the decline of the physicochemical qualities of the samples, and improved the ability of antioxidant enzymes to scavenge reactive oxygen species. Furthermore, reductions in the growth of L. plantarum of only 1.72 log CFU/g were observed after 15 days of storage at 4 °C for samples treated with encapsulated L. plantarum and eugenol. Results suggest the combined encapsulated L. plantarum and eugenol appears to be a promising method to protect fresh-cut apples from food-borne pathogens while maintaining the visual appearance.

Abstract Juice spoilage caused by Alicyclobacillus acidoterrestris has troubled the global manufacturers for many years. Most approaches have failed to detect this bacterium with desirable sensitivity and selectivity because of their inherent drawbacks. In this work, carbon dots (CDs) with bright fluorescence were prepared which can be quenched by the HRP‐catalyzed oxidation product of p‐phenylenediamine, via inner filter effect. Therefore, an unlabeled fluorescence ELISA strategy incorporating CDs as signal reporter was developed for the detection of A. acidoterrestris in apple juice. This approach showed excellent performance on target identification with enhanced specificity, achieving a limit of detection of 3.2 × 102 CFU/mL. It is expected that this method could provide a reliable way for timely identification of A. acidoterrestris, effectively warning against the emergence of juice spoilage incidence.

Abstract Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium genera. It is hepatotoxic, nephrotoxic and carcinogenic. The growing contamination of OTA in wine and grape juice is a great threat to human. In this study, different enzymes were screened for the detoxification of OTA in wine and grape juice. The results indicated that seven enzymes had OTA degradation capacity in the buffer, and the degradation rate of carboxypeptidase A (CPA), lipase, pancreatin and thermolysin were 100%, 100%, 75.72%, and 73.45%, respectively. In grape beverages, pancreatin and CPA showed the most promising result with OTA degradation of 53.24% and 61.56% at 37°C. The LC‐MS/MS analysis further indicated that OTA produced nontoxic OTα and phenylalanine under treatment with three enzymes (carboxypeptidase A, lipase, and pancreatin). Furthermore, pancreatin and CPA had a clarifying effect on wine and grape juice, but had a slight effect on the organic acids and flavor components of them. It suggested that pancreatin and CPA could be used for OTA degradation in grape beverages.

Ochratoxin A (OTA) is a secondary metabolite of several fungi and widely exists in various species of foods. The establishment of effective methods for OTA reduction is a key measure to ensure food processing and human health. This article reviews the current research of OTA reduction by biological approaches, summarizes the characteristics and efficiency of them, and evaluates the transformation pathways and metabolites safety of each degradation technology. The shortcomings of various methods are pointed out and future prospects are also proposed. Biological methods are the most promising approaches for OTA control. The defect of them is the long processing time and the growth of microbial cells may affect the product quality. Therefore, the control of OTA contamination should be conducted according to the food processing and their product types. Besides, it is significant for the exploitation of new strains, enzyme and novel adsorbents.