ACP-DRL: an anticancer peptides recognition method based on deep representation learning.

Cancer, a significant global public health issue, resulted in about 10 million deaths in 2022. Anticancer peptides (ACPs), as a category of bioactive peptides, have emerged as a focal point in clinical cancer research due to their potential to inhibit tumor cell proliferation with minimal side effects. However, the recognition of ACPs through wet-lab experiments still faces challenges of low efficiency and high cost. Our work proposes a recognition method for ACPs named ACP-DRL based on deep representation learning, to address the challenges associated with the recognition of ACPs in wet-lab experiments. ACP-DRL marks initial exploration of integrating protein language models into ACPs recognition, employing in-domain further pre-training to enhance the development of deep representation learning. Simultaneously, it employs bidirectional long short-term memory networks to extract amino acid features from sequences. Consequently, ACP-DRL eliminates constraints on sequence length and the dependence on manual features, showcasing remarkable competitiveness in comparison with existing methods.

Succinate pretreatment attenuates intestinal ischemia-reperfusion injury by inhibiting necroptosis and inflammation via upregulating Klf4.

Intestinal ischemia-reperfusion (I/R) injury is a common pathophysiological process in various diseases, and the disruption of the intestinal barrier composed of tight junction proteins is the initiating factor, which then leads to a large number of bacteria and endotoxins in the intestine into the bloodstream causing stress and distant organ damage. The release of inflammatory mediators and abnormal programmed death of intestinal epithelial cells are important factors of intestinal barrier damage. Succinate is an intermediate product of the tricarboxylic acid cycle with anti-inflammatory and pro-angiogenic activities, but its role in the maintenance of intestinal barrier homeostasis after I/R has not been fully elucidated. In this study, we explored the effect of succinate on intestinal ischemia-reperfusion injury and the possible mechanism of its role by flow cytometry, western blotting, real-time quantitative PCR and immunostaining. The results of pretreatment with succinate in the mouse intestinal I/R model and IEC-6 cells hypoxia-reoxygenation (H/R) model revealed a reduction in tissue damage, necroptosis and associated inflammation due to ischemia-reperfusion. Furthermore, it was found that the protective effect of succinate pretreatment may be associated with the transcriptional upregulation of the inflammatory protein KLF4 and the protective effect of intestinal barrier of succinate was diminished after inhibition of KLF4. Thus, our results suggest that succinate can exert a protective effect in intestinal ischemia-reperfusion injury through upregulation of KLF4 and also demonstrate the potential therapeutic value of succinate pretreatment in acute I/R injury of the intestine.

[An antibacterial peptides recognition method based on BERT and Text-CNN].

Antimicrobial peptides (AMPs) are small molecule peptides that are widely found in living organisms with broad-spectrum antibacterial activity and immunomodulatory effect. Due to slower emergence of resistance, excellent clinical potential and wide range of application, AMP is a strong alternative to conventional antibiotics. AMP recognition is a significant direction in the field of AMP research. The high cost, low efficiency and long period shortcomings of the wet experiment methods prevent it from meeting the need for the large-scale AMP recognition. Therefore, computer-aided identification methods are important supplements to AMP recognition approaches, and one of the key issues is how to improve the accuracy. Protein sequences could be approximated as a language composed of amino acids. Consequently, rich features may be extracted using natural language processing (NLP) techniques. In this paper, we combine the pre-trained model BERT and the fine-tuned structure Text-CNN in the field of NLP to model protein languages, develop an open-source available antimicrobial peptide recognition tool and conduct a comparison with other five published tools. The experimental results show that the optimization of the two-phase training approach brings an overall improvement in accuracy, sensitivity, specificity, and Matthew correlation coefficient, offering a novel approach for further research on AMP recognition.

6'-O-Galloylpaeoniflorin attenuates Helicobacter pylori-associated gastritis via modulating Nrf2 pathway.

As a common disease of the digestive system, chronic gastritis is inflammation of the gastric mucosa caused by various factors. Helicobacter pylori (H. pylori) is one of the main causes of chronic gastritis, which can lead to gastric mucosal damage and gland atrophy, thereby promoting gastrocarcinogenesis. Oxidative stress and the inflammatory response are important mechanisms of H. pylori-induced gastritis. 6'-O-Galloylpaeoniflorin (GPF) is a substance isolated from peony root with antioxidant and anti-inflammatory activities. However, its role and mechanism in the pathogenesis of H. pylori-induced chronic gastritis remain unclear. This study explored the effects of GPF on H. pylori-induced gastric mucosal oxidative stress and inflammation using flow cytometry, western blotting, real-time quantitative PCR, and immunohistochemistry. We found that H. pylori infection increased oxidative stress and expression of inflammatory cytokines in vitro and in vivo and that these outcomes were inhibited by GPF. Furthermore, GPF activated nuclear factor erythroid-related factor-2 (Nrf2) and its downstream target genes in H. pylori-infected GES-1 cells and mice. The anti-inflammatory and antioxidant effects of GPF on H. pylori-infected cells were attenuated by an Nrf2 inhibitor. Taken together, these data suggest that GPF reduces H. pylori-induced gastric mucosa injury by activating Nrf2 signaling and that GPF is a potential candidate for the treatment of H. pylori-associated gastritis.

PTPN6-EGFR Protein Complex: A Novel Target for Colon Cancer Metastasis.

This study investigates the expression of nonreceptor protein tyrosine phosphatase 6 (PTPN6) gene in different colon cancer cells and its effect on malignant biological behavior. The expression level of PTPN6 mRNA in different colon cancer cell lines was detected by qPCR. CCK-8, clone formation assay, scratch assay, and transwell assay were used to detect the effect of knockdown or overexpression of the PTPN6 gene on the malignant biological behavior of colon cancer cells. CO-IP assay was used to detect the interaction protein of PTPN6. PTPN6 was highly expressed in colorectal cancer tissues. High expression of PTPN6 is associated with poor prognosis in patients with colon cancer. PtPN6 knockdown inhibited the proliferation, invasion, migration, and clonogenesis of colorectal cancer LOVO and SW480 cells. At the same time, the knockdown of PTPN6 inhibited the EMT process in colorectal cancer. CO-IP results showed that PTPN6 had a protein-protein interaction with EGFR. Overexpression of EGFR increased the carcinogenic effect of PTPN6. The high expression of the PTPN6 gene can promote the proliferation, migration, and invasion of colon cancer cells. PTPN6 can interact with EGFR. PTPN6-EGFR complex may be an important factor affecting the biological characteristics of colon cancer cells and a potential therapeutic target.

BRCC36 promotes intestinal mucosal barrier injury caused by BMP2 after ischemia reperfusion via inhibiting PPARγ signaling.

As one of the most common pathological changes in trauma and surgery practice, intestinal ischemia-reperfusion (I/R) injury is regarded as a major precipitating factor in the occurrence and development of fatal diseases. BRCA1-BRCA2-containing complex subunit 36 (BRCC36), a deubiquitinase, has been proved important in a variety of pathophysiological processes such as DNA repair, cell cycle regulation, tumorigenesis, and inflammatory response. However, the effect of BRCC36 on intestinal mucosal barrier injury after I/R has not been fully elucidated. Our research found that BRCC36 aggravated intestinal mucosal barrier injury caused by bone morphogenetic protein 2 after I/R by downregulating peroxisome proliferator-activated receptor-γ (PPARγ) signaling. These results suggested that BRCC36/PPARγ axis might serve as a potential therapeutic target for preventing intestinal mucosal barrier injury after I/R.

Safety and feasibility of total laparoscopic radical resection of Siewert type II gastroesophageal junction adenocarcinoma through the left diaphragm and left thoracic auxiliary hole.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is rising every year; however, the mode of operation for Siewert II AEG is still controversial. Accumulating evidence has shown that transabdominal surgery is better than transthoracic surgery for Siewert II AEG with esophageal invasion < 3 cm. In patients with obesity, a large tumor size, and high transection of the esophagus, the transabdominal esophageal hiatus approach for lower mediastinal lymph node dissection and posterior mediastinal anastomosis is difficult. Thus, total laparoscopic radical resection of Siewert II AEG is carried out through the left diaphragm and left chest auxiliary hole for the optimal surgical field of vision and space. In this prospective study, we assessed the feasibility of carrying out the procedure abdominally through the left diaphragm and auxiliary hole. METHODS: Ten patients with Siewert II AEG were recruited between April and June 2019. Siewert II AEG was treated by total laparoscopy through the left diaphragm and left chest auxiliary hole. Clinicopathological features, surgical data, and adverse events were collected and analyzed in this prospective study. RESULTS: The average duration of the operation was 348 ± 37.52 min, lower mediastinal dissection took 20.6 min, the OrVil anastomosis time was 29.8 min, the time necessary to suture the seromuscular layer through the left thoracic auxiliary hole was 11 min, the safety margin was 3.2 cm, and the total number of lymph nodes dissected was 40.6. The number of lower mediastinal lymph nodes dissected was 6.2. The rate of lymph node metastasis in the N110 group was 9 ± 12.45%, and the average intraoperative blood loss was 170 ± 57.47 mL. No anastomotic leakage or anastomotic stricture occurred after the operation. The time of intestinal function recovery was 2 days, and the first time of enteral nutrition through a jejunal nutrition tube was 2.4 days. No tumor recurrence was found in 10 patients at 1 year postoperatively. CONCLUSION: Total laparoscopic radical resection through the left diaphragm and left thoracic auxiliary hole for Siewert II AEG patients is feasible and safe. Thus, it may be a good surgical alternative for patients with esophageal tumors invading less than 3 cm. TRIAL REGISTRATION: ChiCTR, ChiCTR2000034286. Registered 8 July 2020, http://www.chictr.org.cn/showproj.aspx?proj=55866 .

Da Vinci robot-assisted resection to treat abdominal ectopic thyroid: a case report and literature review.

Although ectopic thyroid can be found in thoracic locations, the discovery of abdominal ectopic thyroid is often an accidental event. Moreover, abdominal ectopic thyroid is easily misdiagnosed due to the rarity of these cases and the difficulties in the preoperative diagnosis process. Thus, we aimed to assess the prevalence and features of abdominal ectopic thyroid and to highlight the current knowledge about the clinical characteristics and management of this condition by analyzing a case report of abdominal ectopic thyroid and reviewing the literature. A 70-year-old woman with a 3-year history of gradually increasing abdominal distension in the right lower quadrant of the abdomen was admitted to the hospital. Contrast-enhanced computed tomography (CT) of the abdomen revealed a retroperitoneal mass. The patient underwent Da Vinci robotic surgery, and the retroperitoneal mass was completely resected. Subsequently, the pathologic diagnosis of the mass was ET. The patient had no discomfort or symptoms when she was discharged from the hospital and at the postoperative 1, 3, 6, 9 and 12 months follow-up. The summary of literature review suggested that abdominal ectopic thyroid is still rare although there are some reports. Nonetheless, the cause of abdominal ectopic thyroid is unclear, and abdominal ectopic thyroid has the following characteristics: more common in women than in men, asymptomatic in the majority of the cases, difficult to diagnose, and found by excluding metastasis. Most ectopic thyroid is treated with surgery, and minimally invasive techniques have been increasingly performed. This is the first report on Da Vinci robotic resection for large rare retroperitoneal ET, and this case highlights that ET should be considered when patients present with similar imaging findings in the abdomen.

Total laparoscopic transabdominal-transdiaphragmatic approach for treating Siewert II tumors: a prospective analysis of a case series.

BACKGROUND: Although the morbidity of gastric cancer has decreased, the incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing. Furthermore, no consensus exists on which surgical approach should be applied for Siewert type II AEG. The purpose of our study was to evaluate the technical safety and feasibility of a new surgical approach. METHODS: Sixty patients with Siewert type II AEG underwent laparoscopic total gastrectomy with the total laparoscopic transabdominal-transdiaphragmatic (TLTT) approach, which needs an incision in the diaphragm. RESULTS: The median operative time, reconstruction time, and estimated blood loss were 214.8 ± 41.6 min, 29.40 ± 7.1 min, and 209.0 ± 110.3 ml, respectively. All of the patients had negative surgical margins. CONCLUSION: There were no intraoperative complications or conversions to open surgery. Our surgical procedure provides a unique option for the safe application of laparoscopic lower mediastinal lymph node dissection and gastrointestinal reconstruction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800014336. Registered on 31 December 2017 - Prospectively registered, http://www.chictr.org.cn/edit.aspx?pid=23111&htm=4 .

Transanal total mesorectal excision (TaTME) using flexible endoscope with laparoscopic assistance: a pilot study in porcine models.

BACKGROUND: Transanal total mesorectal excision (TaTME) is routinely performed to excise low rectal tumors. TaTME often relies on transanal endoscopic microsurgery (TEM) or transanal minimally invasive surgery (TAMIS) platform, all using rigid endoscopes. Our study reported a novel approach to TaTME which was completed using flexible endoscope, and we named it F-TaTME. METHODS: The feasibility of rectum resection using F-TaTME was evaluated in five pigs. Firstly, the superior rectal artery and vein were managed under the assistance of laparoscopy. Secondly, the flexible endoscope was used to complete the full-thickness rectotomy and rectal mobilization. Finally, the specimen was removed and the manual colon-rectal anastomosis was performed under direct vision. RESULTS: F-TaTME was accomplished in all 5 pigs. The mean procedure time was 136.6 min (97-162 min). The mean length from the lower edge of the lesion to circumferential dissection line was 1.4 cm (1.0-1.8 cm) and mean length of exteriorized rectum was 12.6 cm (11-14 cm). No injury to colorectal wall, adjacent pelvic or abdominal organs was found. CONCLUSIONS: Our preliminary data suggested that F-TaTME may be a feasible method for TaTME.

Adaptation of the FK506 binding protein 1B to hibernation in bats.

Hibernation is an adaptive strategy used by some animals to cope with cold and food shortage. The heart rate, overall energy need, body temperature, and many other physiological functions are greatly reduced during torpor but promptly return to normal levels upon arousal. The heartbeat of torpid bats can be hundreds fold lower than that of active bats, indicating that hibernating bats have a remarkable ability to control excitation-contraction coupling in cardiac muscle. FKBP1B (calstabin 2), a peptidyl-prolyl cis-trans isomerase, is critical for the regulation of excitation-contraction coupling. Whether FKBP1B is adapted to hibernation in bats is not known. Evolutionary analyses showed that the ω values of the Fkbp1b genes of 25 mammalian species are all less than 1, and amino acid sequence alignments revealed that FKBP1B proteins are highly conserved in mammals. The expression of the Fkbp1b gene was found to be elevated at both mRNA and protein levels in two distantly related bats (Rhinolophus ferrumequinum in Yinpterochiroptera and Myotis ricketti in Yangochiroptera) during torpor. Transcription factors such as YY1 and SPs were bioinformatically determined to have a higher binding affinity to the potential regulatory regions of Fkbp1b genes in hibernating than in non-hibernating mammals. This study provides new insights into the molecular evolution of Fkbp1b in adaptation to bat hibernation.

Multiple adaptive losses of alanine-glyoxylate aminotransferase mitochondrial targeting in fruit-eating bats.

The enzyme alanine-glyoxylate aminotransferase 1 (AGT) functions to detoxify glyoxylate before it is converted into harmful oxalate. In mammals, mitochondrial targeting of AGT in carnivorous species versus peroxisomal targeting in herbivores is controlled by two signal peptides that correspond to these respective organelles. Differential expression of the mitochondrial targeting sequence (MTS) is considered an adaptation to diet-specific subcellular localization of glyoxylate precursors. Bats are an excellent group in which to study adaptive changes in dietary enzymes; they show unparalleled mammalian dietary diversification as well as independent origins of carnivory, frugivory, and nectarivory. We studied the AGT gene in bats and other mammals with diverse diets and found that the MTS has been lost in unrelated lineages of frugivorous bats. Conversely, species exhibiting piscivory, carnivory, insectivory, and sanguinivory possessed intact MTSs. Detected positive selection in the AGT of ancestral fruit bats further supports adaptations related to evolutionary changes in diet.

Recent loss of vitamin C biosynthesis ability in bats.

The traditional assumption that bats cannot synthesize vitamin C (Vc) has been challenged recently. We have previously shown that two Old World bat species (Rousettus leschenaultii and Hipposideros armiger) have functional L-gulonolactone oxidase (GULO), an enzyme that catalyzes the last step of Vc biosynthesis de novo. Given the uncertainties surrounding when and how bats lost GULO function, exploration of gene evolutionary patterns is needed. We therefore sequenced GULO genes from 16 bat species in 5 families, aiming to establish their evolutionary histories. In five cases we identified pseudogenes for the first time, including two cases in the genus Pteropus (P. pumilus and P. conspicillatus) and three in family Hipposideridae (Coelops frithi, Hipposideros speoris, and H. bicolor). Evolutionary analysis shows that the Pteropus clade has the highest ω ratio and has been subjected to relaxed selection for less than 3 million years. Purifying selection acting on the pseudogenized GULO genes of roundleaf bats (family Hipposideridae) suggests they have lost the ability to synthesize Vc recently. Limited mutations in the reconstructed GULO sequence of the ancestor of all bats contrasts with the many mutations in the ancestral sequence of recently emerged Pteropus bats. We identified at least five mutational steps that were then related to clade origination times. Together, our results suggest that bats lost the ability to biosynthesize vitamin C recently by exhibiting stepwise mutation patterns during GULO evolution that can ultimately lead to pseudogenization.