Fibrotic Matrix Induces Mesenchymal Transformation of Epithelial Cells in Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.

A new dimethylsulfoniopropionate lyase of the cupin superfamily in marine bacteria.

Dimethylsulfoniopropionate (DMSP) is a marine organosulfur compound with important roles in stress protection, marine biogeochemical cycling, chemical signalling and atmospheric chemistry. Diverse marine microorganisms catabolize DMSP via DMSP lyases to generate the climate-cooling gas and info-chemical dimethyl sulphide. Abundant marine heterotrophs of the Roseobacter group (MRG) are well known for their ability to catabolize DMSP via diverse DMSP lyases. Here, a new DMSP lyase DddU within the MRG strain Amylibacter cionae H-12 and other related bacteria was identified. DddU is a cupin superfamily DMSP lyase like DddL, DddQ, DddW, DddK and DddY, but shares <15% amino acid sequence identity with these enzymes. Moreover, DddU proteins forms a distinct clade from these other cupin-containing DMSP lyases. Structural prediction and mutational analyses suggested that a conserved tyrosine residue is the key catalytic amino acid residue in DddU. Bioinformatic analysis indicated that the dddU gene, mainly from Alphaproteobacteria, is widely distributed in the Atlantic, Pacific, Indian and polar oceans. For reference, dddU is less abundant than dddP, dddQ and dddK, but much more frequent than dddW, dddY and dddL in marine environments. This study broadens our knowledge on the diversity of DMSP lyases, and enhances our understanding of marine DMSP biotransformation.

Utilizing Topological Insulator Two-Dimensional Bismuth for Ultrasensitive Acoustic Detection.

Topological insulators (TIs) are characterized by a full insulating gap in the bulk and gapless edge or surface states, which have attracted tremendous attention. 2D Bi (110), as a typical TI, is of particular interest due to its low symmetry structure and topologically protected and spin-momentum-locked Dirac surface states. However, the material's potential applications are hindered by difficulties in fabrication, due to its strong semi-metallic bonding and poor stability. In this study, a novel electrochemical intercalation method for the fabrication of ultrathin Bi (110) nanosheets with the highest yield ever reported is presented. These nanosheets are stabilized through cathodic exfoliation in a reductive environment and further modification with polymer ionic liquids. The versatility of these nanosheets is demonstrated by fabricating flexible acoustic sensors with ultrahigh sensitivity. These sensors can even detect sounds as quiet as 45 dB. Furthermore, these sensors are utilized for acoustic-to-electric energy conversion and information transfer. This work offers a promising approach for scalable fabrication and preservation of ultrathin 2D TI Bi (110) nanosheets and paves the way for their integration into smart devices.

Base editing for reprogramming cyanobacterium Synechococcus elongatus.

Cyanobacteria can directly convert carbon dioxide (CO2) at the atmospheric level to biofuels, value-added chemicals and food products, making them ideal candidates to alleviate global climate change. Despite decades-long pioneering successes, the development of genome-editing tools, especially the CRISPR-Cas-based approaches, seems to lag behind other microbial chassis, slowing down the innovations of cyanobacteria. Here, we adapted and tailored base editing for cyanobacteria based on the CRISPR-Cas system and deamination. We achieved precise and efficient genome editing at a single-nucleotide resolution and demonstrated multiplex base editing in the model cyanobacterium Synechococcus elongatus. By using the base-editing tool, we successfully manipulated the glycogen metabolic pathway via the introduction of premature STOP codons in the relevant genes, building engineered strains with elevated potentials to produce chemicals and food from CO2. We present here the first report of base editing in the phylum of cyanobacteria, and a paradigm for applying CRISPR-Cas systems in bacteria. We believe that our work will accelerate the metabolic engineering and synthetic biology of cyanobacteria and drive more innovations to alleviate global climate change.

The passive diffusion improvement of Vitamin B12 intestinal absorption by Gelucire that fit for commercialized production.

Vitamin B12 (VB12) is a vital micronutrient to maintain the normal state of the hematopoietic system. It must be obtained from the diet since the human body cannot synthesize it. Moreover, the absorption of VB12 needs to be mediated by intrinsic factor on the gastrointestinal (GI) track. The abnormalities in the stomach or lack of such intrinsic factors may result in poor oral absorption of VB12. However, the very advanced formulation strategies were generally very costly and still in the development stage. Thus, the objectives of the present study were to increase the VB12 intestinal absorption by conventional excipients of Gelucire 44/14 (G44/14) or Labrasol, which could be potentially formulated as a cost effect balanced product. The in vitro Caco-2 cell model was applied for the absorption study. A novel VB12 solid dispersion was subsequently prepared and further characterized by Differential scanning calorimetry, Fourier transform infrared spectroscopy, and Scanning electron microscopy, respectively. The membrane permeability of the VB12 solid dispersion was finally evaluated using ex vivo rat everted gut sac method. The results suggested that G44/14 could significantly enhance the intestinal absorption of VB12 via P-glycoprotein inhibition in vitro (P < 0.01). The membrane permeability of VB12could be significantly (P < 0.01) improved by G44/14-VB12 solid dispersion at a proportion of carrier: drug ratio of 20:1.The liquidfied solid dispersion was finally directly filled in the hard gelatin capsules. In conclusion, the cheap and simplified process of VB12 complex prepared by G44/14 could potentially increase VB12 intestinal absorption, which may be liable to commercial manufacturing.

Sintilimab in Patients with Previously Treated Metastatic Neuroendocrine Neoplasms.

BACKGROUND: Neuroendocrine neoplasms (NENs) are a group of diseases that show high heterogeneity but have limited treatment options. This phase I study evaluated the safety and efficacy of sintilimab, anti-PD-1 monoclonal antibody, in treating advanced NENs. METHODS: We prospectively enrolled patients pathologically diagnosed with NENs after standard treatment failure. Neuroendocrine neoplasms were classified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine cancers (NECs). Every patient received sintilimab, and response was assessed every 9 weeks. RESULTS: Twenty-four patients with a median age of 57.0 years were enrolled from November 2016 to 2017. The median Ki-67 index was 60%. Five patients had NET, 1 had NET G3, 17 had NEC, and 1 had mixed adenocarcinoma-neuroendocrine carcinoma. The most common primary tumor sites were the pancreas and gastrointestinal tract in 7 and 10 patients, respectively. In phase Ia trial, 2 patients received sintilimab 1 mg/kg every 2 weeks, one received 3 mg/kg every 2 weeks, and 21 patients enrolled in the phase Ib trial received 200 mg every 3 weeks. The objective response rate was 20.8% in all enrolled patients and 27.8% in NEC patients. The median progression-free survival was 2.2 and 2.1 months in patients with NET and NEC, respectively. The median OS was not applicable (NA) and 10.8 months (95% CI, 4.3, NA) with NET and NEC, respectively. The duration of response (DOR) was not reached, with a median follow-up time of 20.7 months. Treatment-related adverse events (TRAE) occurred in 17 (70.8%) patients. The most frequent TRAE was thyroid dysfunction (41.7%), and a grade 3 pulmonary infection occurred in 1 patient. The programmed cell death 1-ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) rate was 18.8% (3 out of 16) and the expression of PD-L1 did not correlate with response. CONCLUSION: Sintilimab was well-tolerated and showed encouraging response in NECs. CLINICALTRIALS.GOV IDENTIFIER: NCT02937116.

Hepatic metastasis from perianal Paget's disease without identified underlying carcinoma: a case report.

BACKGROUND: Perianal Paget's disease (PPD) is a rare malignancy, often associated with an underlying adenocarcinoma and a poor prognosis. CASE PRESENTATION: A 69-year-old female was presented with a history of perianal pruritus for 6 months and enlarged inguinal lymph nodes in the left side. Paget cells were confirmed by pathology after a wide excision of perianal skin. Radiotherapy was performed covering the bilateral inguinal lymphatic drainage area. Hepatic metastasis was found 8 months after surgery. Hepatic artery embolization (HAE) and high-intensity focused ultrasound therapy (HIFU) were performed successively. However, hepatic metastasis happened again 3 months later. Ultrasound-guided percutaneous radiofrequency ablation (PRFA) was carried out and various means of inspection could not identify the primary tumor. In the case of rapid progression of the tumor, we gave the patient chemotherapy regimens of XELOX. After 4 cycles of chemotherapy, the tumor marker went down continuously and the hepatic metastasis stayed stable. CONCLUSIONS: Hepatic metastasis from perianal Paget's disease without identified underlying carcinoma may benefit from XELOX on the basis of adenocarcinoma.

microRNA let-7i-5p aggravates kidney fibrosis via targeting GALNT1.

Renal fibrosis poses critical health problem. We aimed to investigate role of let-7i-5p in renal fibrosis. In silico reproduction of Mouse Kidney FibrOmics browser was used to identify potential target of let-7i-5p. In vivo validation was conducted in C57BL/6 mice with unilateral ureteral obstruction (UUO) and folic acid (FA) induction. In vitro validation was performed in transforming growth factor (TGF)-ß1-treated HK-2 cells. Mimics and inhibitors of let-7i-5p, and target gene polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1) were monitored by RT-PCR and Western blotting. Fibrosis markers, injury markers, and house-keeping genes were evaluated. Levels of interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α in serum and media were measured by ELISA. In silico analysis showed gradual increase of let-7i-5p and decrease of GALNT1 over time and the combination was validated both in mouse and human miR-gene target prediction databases. Expression of GALNT1 decreased while expression of let-7i-5p increased in renal tissues of both UUO and FA mice. Serum IL-6, IL-1ß, and TNF-α levels were elevated in vivo. In vitro models revealed negative correlation between expression levels of let-7i-5p and GALNT1. Overexpression of let-7i-5p inhibited GALNT1 expression and reduced release of inflammatory factors. In conclusion, overexpression of GALNT1 may combat the inflammation induced by let-7i-5p.

The inactivation of the non-enveloped enterovirus 71 (EV71) by a novel disinfectant gel formulation for topical use.

BACKGROUND: Hand-foot-mouth disease may cause severe central nervous system complications and even death, that is induced mainly by enterovirus 71 (EV71), which is a non-enveloped virus. Inactivation of the EV71 on hands could effectively inhibit the transmission. However, the inactivations of the EV71 by conventional disinfectants including the alcohols are poor, due to the high stability of the EV71. A novel pyridyl imidazolidinone compound (TJAB1099) was designed to specifically inhibit EV71 replication in vitro. It may potentially be developed as formulations applied on hands for EV71 transmission control. METHODS: The stress stability of TJAB1099 was first evaluated after storing in high temperature (60 °C, RH 10%), high humidity (25 °C, RH90%), and the high-intensity photolysis (4500 Lx ± 500 Lx) for 15 days, respectively. A wash-free antimicrobial gel containing the TJAB1099 was developed using the copolymer carrier. The antiviral activity, the acute oral toxicity, and the local irritation of the antimicrobial gel were evaluated accordingly. RESULTS: The results indicated that the TJAB1099 was stable during the storage in high temperature and humidity. However, a significant change (p < .0001) was detected when TJAB1099 stored in the high-intensity photolysis. The antimicrobial gel containing 1 µM TJAB1099 could inhibit EV71 significantly higher than the ethanol (75%) (p < .0001) and commercialized disinfectant products (p < .0001). The results of acute oral toxicity and the local irritation suggest that the TJAB1099 containing antimicrobial gel was not causing skin irritations and acute oral toxicity symptoms. CONCLUSIONS: The results suggest that the antimicrobial gel containing TJAB1099 was safe and could effectively inhibit EV71 transmission in vitro.

[Efficacy of Oral Corticosteroids in Preventing Esophageal Stenosis after Large Area Endoscopic Submucosal Tunnel Dissection].

OBJECTIVE: To evaluate the efficacy of oral corticosteroids in preventing esophageal stenosis after large area esophageal endoscopic submucosal tunnel dissection (ESTD). METHODS: The patients undertook esophageal ESTD were included from January 2014 to January 2018. The inclusion criteria was single lesion of esophageal early esophagus cancer with the extent more than 3/4 of circumferential degree. According to the inclusion time, the patients were divided into the trial group (ESTD + oral corticosteroids) and the control group (simple ESTD). The incidence of the total esophageal stenosis, intractable esophageal stenosis, the remission rate of dysphagia and the period from the dysphagia present were observed and compared in the two groups. RESULTS: A total of 101 cases of esophageal ESTD patients were included. There were 48 cases in the trial group, 28 cases of male and 20 cases of female, with an average age of (62.98±7.52) years; 53 cases in the control group, 28 cases of male and 25 cases of female, with an average age of (62.67±8.04) years. The rate of intractable esophageal stenosis in the trial group was lower than that in the control group (6.25% vs. 20.75%, P<0.05). The average endoscopic treatment times in the non-refractory stenosis patients in the trial group were significantly less than those in the control group 〔(1.85±0.27) times vs. (3.24±0.49) times, P<0.05〕, and the occurrence time of esophageal stenosis in the trial group was 51.06 d after ESTD, significantly later than that in the control group (29.12 d, P<0.05). CONCLUSIONS: Oral corticosteroids can effectively reduce the degree of esophageal stenosis after large area ESTD, as well as the incidence of intractable esophageal stenosis and the number of endoscopic treatment in non-refractory esophageal stenosis patients.

A comparative study of delta-shaped and conventional Billroth I anastomosis after laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: Delta-shaped anastomosis (DA) is a newly developed intracorporeal gastroduodenostomy. This meta-analysis is performed to compare the safety, feasibility and clinical outcomes of DA with conventional extracorporeal Billroth I anastomosis (B-I) after laparoscopic distal gastrectomy for gastric cancer. METHODS: Both randomized controlled trials (RCTs) and nonrandomized cohort studies comparing outcomes of DA and B-I after laparoscopic distal gastrectomy for gastric cancer were searched in electronic database. Surgical outcomes, postoperative recovery, postoperative complications and outcomes were pooled and compared by meta-analysis using RevMan 5.3 software. Weighted mean differences (WMDs), odds ratios and risk differences were calculated with 95% confidence intervals (CIs). P values of <0.05 were considered statistically significant. RESULTS: Eight nonrandomized cohort studies of 2450 patients were included. Meta-analysis showed significantly less blood loss (WMD -28.72; 95% CI -49.21 to -8.23; P = 0.006), more lymph nodes retrieved (WMD 3.23; 95% CI 0.86-5.61; P = 0.008), shorter time to first soft diet (WMD -0.34; 95% CI -0.47 to -0.21, P < 0.00001), less pain and analgesic use (WMC -0.29; 95% CI -0.56 to -0.02; P = 0.03) in DA than in B-I. Both methods had similar operative time, resection margin, time to first flatus, length of hospital stay and rate of complications. Most of the postoperative symptoms were comparable between groups. The subgroup of obese patient showed more favorable outcomes in DA, and the learning curve of DA is steep. CONCLUSION: DA is a safe and feasible reconstruction method after laparoscopic distal gastrectomy, with comparable postoperative surgical outcomes, postoperative complications comparing to B-I. DA is less invasive with quicker resume of diet than B-I, especially for the obese patients.

Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach.

AIM: Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. METHODS: The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine (TCM) network pharmacology platform. The anti-tumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. RESULTS: The nuciferine target profile was enriched with signaling pathways and biological functions, including "regulation of lipase activity", "response to nicotine" and "regulation of cell proliferation". Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine (0.8 mg/mL) markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine (0.05 mg/mL) significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine (9.5 mg/mL, ip, 3 times a week for 3 weeks) significantly decreased the weight of SY5Y and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. CONCLUSION: By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels.

Diagnosis and Treatment of Duodenal Injury: A Clinical Analysis.

BACKGROUND/AIMS: Duodenal injuries do not often occur and are usually difficult to be diagnosed or treated. METHODOLOGY: To summarize the experience in managing duodenal injuries and determine some prognostic factors, we conducted a retrospective review on 42 cases of duodenal injuries including 17 traumatic (blunt 31.0%, penetrating 9.5%) and 25 iatrogenic (59.5%) ones, which were admitted to our hospital from 1993 to 2013. RESULTS: The mortality rate was 23.8% (n = 10). Main cause of late death was multiple system organ failure and infection. Senility and high APACHE II score were both correlated with mortality rate (P < 0.01 and P < 0.05 respectively). High morbidity and mortality rate were more likely to be associated with those had long delays in treatment or injury in the second part of the duodenum (P < 0.05). The number of associated injuries affected mortality rate (P < 0.05). For traumatic injuries, the mechanism of injury, method of initial surgical management, Organ Injury Scale and Abbreviated Injury Scale were not related to patients' outcome (P > 0.05). CONCLUSIONS: These findings indicated that early diagnosis and timely treatment were of great clinical value. Primary repair with an effective diversion was practicable. Age and APACHE II Score were the independent prognostic factors.

[Neuroprotective effects of paeonol in a cell model of Parkinson disease].

OBJECTIVE: To investigate the effects of paeonol on neuron cell model of Parkinson disease (PD). METHODS: The cell model of Parkinson disease was induced by treatment of 1-Methyl-4-phenylpyridinium (MPP+) in PC12 cells, the PD model cells were treated with 1 µmol/L, 3 µmol/L or 9 µmol/L paeonol for 24h, respectively. Cell viability and LDH leakage were detected by MTT and lactate dehydrogenase (LDH) assay; the apoptosis of PC12 cells was assessed by Hoechst 33258 staining and flow cytometry; reactive oxygen species (ROS) production was detected by DCFH-DA method; and the ratio of Bax/Bcl-2 and activation of caspase-3 were determined by Western blotting. RESULTS: MPP+ treatment significantly reduced cell viability, increased LDH leakage, enhanced the proportion of apoptotic cells and ROS production. In addition, MPP+ treatment dramatically increased the Bax/Bcl-2 ratio, and the activation of caspase-3. Compared to PD model group, paeonol treatment significantly enhanced cell viability, decreased LDH leakage, inhibited the proportion of apoptotic cells and ROS production, reduced the Bax/Bcl-2 ratio and the activated caspase-3 protein. CONCLUSION: Paeonol can prevent PC12 cells from apoptosis induced by MPP+, and the mechanism may be associated with the down-regulation of ROS production, Bax/Bcl-2 ratio and Caspase-3 activation.

Exploring the relationship between metal ion valency and electron transfer in copigmentation processes of cyanidin-3-O-glucoside in simulated fruit wine solutions.

In this experiment, five metal ions (K+, Mg2+, Al3+, Ga3+, and Sn4+) were utilized as copigments to investigate their copigmentation processes with cyanidin-3-O-glucoside (C3OG) in simulated fruit wine solutions. The color characteristics were analyzed using Glories and CIELAB methods, and the copigmentation effects were determined spectrophotometrically. Thermodynamic parameters, including the equilibrium constant (K) and standard Gibbs free energy (ΔG°), were calculated to comprehend the binding affinity between metal ions and C3OG. Ultra-fast femtosecond spectroscopy was employed to monitor the photoinduced electron transfer process between C3OG and cations. Theoretical calculations were also conducted to support experimental findings. The results revealed that the presence of metal ions significantly enhanced the color intensity of C3OG in simulated fruit wine solutions. Higher valency cations, particularly Sn4+, Ga3+, and Al3+, exhibited superior copigmentation effects, resulting in significant bathochromic and hyperchromic changes. Thermodynamic analysis confirmed that the interaction between C3OG and metal ions was spontaneous and exothermic. Ultra-fast femtosecond spectroscopy demonstrated that electron transfer from C3OG to metal ions occurred, with the efficiency of transfer being dependent on valency. Theoretical calculations corroborated the experimental results by highlighting the role of metal ions in stabilizing C3OG/metal complexes through electron transfer. The findings presented in this study contribute to a more comprehensive understanding of pigment/metal complexes and the underlying chemistry behind fruit wine color. Furthermore, it advances the theoretical foundation of copigmentation and broadens its applications in the beverage industry.

Phytoplankton-derived polysaccharides and microbial peptidoglycans are key nutrients for deep-sea microbes in the Mariana Trench.

BACKGROUND: The deep sea represents the largest marine ecosystem, driving global-scale biogeochemical cycles. Microorganisms are the most abundant biological entities and play a vital role in the cycling of organic matter in such ecosystems. The primary food source for abyssal biota is the sedimentation of particulate organic polymers. However, our knowledge of the specific biopolymers available to deep-sea microbes remains largely incomplete. One crucial rate-limiting step in organic matter cycling is the depolymerization of particulate organic polymers facilitated by extracellular enzymes (EEs). Therefore, the investigation of active EEs and the microbes responsible for their production is a top priority to better understand the key nutrient sources for deep-sea microbes. RESULTS: In this study, we conducted analyses of extracellular enzymatic activities (EEAs), metagenomics, and metatranscriptomics from seawater samples of 50-9305 m from the Mariana Trench. While a diverse array of microbial groups was identified throughout the water column, only a few exhibited high levels of transcriptional activities. Notably, microbial populations actively transcribing EE genes involved in biopolymer processing in the abyssopelagic (4700 m) and hadopelagic zones (9305 m) were primarily associated with the class Actinobacteria. These microbes actively transcribed genes coding for enzymes such as cutinase, laccase, and xyloglucanase which are capable of degrading phytoplankton polysaccharides as well as GH23 peptidoglycan lyases and M23 peptidases which have the capacity to break down peptidoglycan. Consequently, corresponding enzyme activities including glycosidases, esterase, and peptidases can be detected in the deep ocean. Furthermore, cell-specific EEAs increased at 9305 m compared to 4700 m, indicating extracellular enzymes play a more significant role in nutrient cycling in the deeper regions of the Mariana Trench. CONCLUSIONS: Transcriptomic analyses have shed light on the predominant microbial population actively participating in organic matter cycling in the deep-sea environment of the Mariana Trench. The categories of active EEs suggest that the complex phytoplankton polysaccharides (e.g., cutin, lignin, and hemicellulose) and microbial peptidoglycans serve as the primary nutrient sources available to deep-sea microbes. The high cell-specific EEA observed in the hadal zone underscores the robust polymer-degrading capacities of hadal microbes even in the face of the challenging conditions they encounter in this extreme environment. These findings provide valuable new insights into the sources of nutrition, the key microbes, and the EEs crucial for biopolymer degradation in the deep seawater of the Mariana Trench. Video Abstract.

Erratum to: "Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p".

[This corrects the article DOI: 10.1515/med-2021-0319.].

ß-sitosterol alleviates dextran sulfate sodium-induced experimental colitis via inhibition of NLRP3/Caspase-1/GSDMD-mediated pyroptosis.

Background: Inflammation-related NLRP3/Caspase-1/GSDMD-mediated pyroptosis is involved in the progression of ulcerative colitis (UC). ß-sitosterol (SIT) was reported to have anti-inflammatory effects on experimental colitis, while the regulation of SIT on pyroptosis is unclear. Therefore, the present study aimed to define the protective and healing effects of SIT on dextran sulfate sodium (DSS)-induced experimental UC rats and human epithelial colorectal adenocarcinoma cells (Caco-2) and explore the underlying mechanisms that are responsible for its effects on NLRP3/Caspase-1/GSDMD-mediated pyroptosis in UC. Methods: UC model rats were established by oral 4% DSS. Following colitis injury, the animals received SIT (doses of 50, 100, and 200 mg/kg) treatment for 2 weeks. For in vitro study, we exposed Caco-2-50 mg/mL DSS with or without SIT (concentrations of 8 and 16 µg/mL). Disease activity index (DAI) and histopathological injury were assessed in vivo. Activation proteins of nuclear factor kappa B (NF-κB) signaling axis, and tight junction-related proteins of zonula occludens-1 (ZO-1) and occludin were detected in colon tissues. TNF-α, IL-1ß, and IL-18 in serum and cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Changes in NLRP3/Caspase-1/GSDMD-mediated pyroptosis signaling pathway activation were analyzed both in tissues and cells. Results: Our findings suggested that SIT treatment attenuated the severity of 4% DSS-induced UC by protecting rats from weight and colon length loss, and macroscopic damage. SIT also reduced proinflammatory factors production (TNF-α, IL-1ß, and IL-18) in serum and cell supernatant. Mechanistically, SIT downregulated the expression levels of pyroptosis-related proteins including Caspase-1, cleaved-Caspase-1, NLRP3, GSDMD, and GSDMD-N in colon tissues and Caco-2 cells. Further analysis indicated that SIT maintained the colonic barrier integrity by enhancing the protein expression of ZO-1 and occludin. Conclusion: We confirmed that SIT exerts protective and therapeutic effects on DSS-induced colitis injury by suppressing NLRP3/Caspase-1/GSDMD-mediated pyroptosis and inflammation response. These findings demonstrated that SIT could be a potential medication for UC treatment.

First report of prevalence and assemblage analysis of Giardia duodenalis in pigs from Guangxi Zhuang Autonomous Region, southern China.

Giardia duodenalis is a common intestinal protozoan that can cause diarrhea and intestinal disease in animals and in humans. However, the prevalence and assemblages of G. duodenalis in pigs from Guangxi Zhuang Autonomous Region have not been reported. In this study, a total of 724 fecal samples (201 from nursery pigs, 183 from piglets, 175 from breeding pigs, and 165 from fattening pigs) were obtained in four areas of the region (Nanning, Yulin, Hezhou, and Guigang). The gene of the small subunit ribosomal RNA (SSU rRNA) of G. duodenalis was amplified by nested PCR. The results show that the prevalence of G. duodenalis in pigs was 3.59% (26/724), of which 14 samples belonged to assemblage A (53.85%) and 12 samples belonged to assemblage E (46.15%). The infection rates of G. duodenalis in Hezhou, Yulin, Nanning, and Guigang were 0%, 0.7%, 10.8% and 1.1%, respectively (χ2 = 45.616, p < 0.01); whereas 5.1% of breeding pigs, 6.0% of piglets, 2.4% of fattening pigs, and 1.0% of nursery pigs were infected with G. duodenalis (χ2 = 8.874, p < 0.05). The SSU rRNA-positive samples were amplified by PCR based on the ß-giardin (bg), glutamate dehydrogenase (gdh), and triphosphate isomerase (tpi) genes. Ten, eight and seven positive samples were detected, respectively. Based on phylogenetic analysis of the three genetic loci sequences, a multilocus genotyping A1 was found. The findings of this study provide basic data for the development of prevention and control of G. duodenalis infections in pigs and humans in the Guangxi Zhuang Autonomous Region.

Title: Premier rapport sur la prévalence et l'analyse des assemblages de Giardia duodenalis chez les porcs de la région autonome Zhuang du Guangxi, dans le sud de la Chine. Abstract: Giardia duodenalis est un protozoaire intestinal commun qui peut provoquer des diarrhées et des maladies intestinales chez les animaux et les humains. Cependant, la prévalence et les assemblages de G. duodenalis chez les porcs de la région autonome Zhuang du Guangxi n'ont pas été rapportés. Dans cette étude, un total de 724 échantillons fécaux (201 provenant de jeunes porcelets, 183 de porcelets, 175 de porcs reproducteurs et 165 de porcs à l'engrais) ont été obtenus dans quatre zones de la région (Nanning, Yulin, Hezhou et Guigang). Le gène de la petite sous-unité de l'ARN ribosomal (ARNr SSU) de G. duodenalis a été amplifié par PCR nichée. Les résultats ont montré que la prévalence de G. duodenalis chez les porcs était de 3,59 % (26/724), dont 14 échantillons appartenaient à l'assemblages A (53,85 %) et 12 échantillons à l'assemblage E (46,15 %). Les taux d'infection par G. duodenalis à Hezhou, Yulin, Nanning et Guigang étaient respectivement de 0, 0,7 %, 10,8 % et 1,1 % (χ2 = 45,616, p < 0,01), alors que 5,1 % des porcs reproducteurs, 6,0 % des porcelets, 2,4 % de porcs à l'engrais et 1,0 % des jeunes porcelets étaient infectés par G. duodenalis (χ2 = 8,874, p < 0,05). Les échantillons positifs pour l'ARNr SSU ont été amplifiés par PCR basée sur les gènes de la ß-giardine (bg), de la glutamate déshydrogénase (gdh) et de la triphosphate isomérase (tpi), et dix, huit et sept échantillons positifs ont été détectés, respectivement. Sur la base de l'analyse phylogénétique des trois séquences de loci génétiques, un génotypage multilocus A1 a été trouvé. Les résultats de cette étude fournissent des données de base pour le développement de la prévention et du contrôle des infections à G. duodenalis chez les porcs et les humains dans la région autonome Zhuang du Guangxi.