Autophagy and its role in gastrointestinal diseases.

Gastrointestinal disorders encompass a spectrum of conditions affecting various organs within the digestive system, such as the esophagus, stomach, colon, rectum, pancreas, liver, small intestine, and bile ducts. The role of autophagy in the etiology and progression of gastrointestinal diseases has garnered significant attention. This paper seeks to evaluate the impact and mechanisms of autophagy in gastrointestinal disorders by synthesizing recent research findings. Specifically, we delve into inflammation-related gastrointestinal conditions, including ul-cerative colitis, Crohn's disease, and pancreatitis, as well as gastrointestinal cancers such as esophageal, gastric, and colorectal cancers. Additionally, we provide commentary on a recent publication by Chang et al in the World Journal of Gastroenterology. Our objective is to offer fresh perspectives on the mechanisms and therapeutic approaches for these gastrointestinal ailments. This review aims to offer new perspectives on the mechanisms and therapeutic strategies for gastrointestinal disorders by critically analyzing relevant publications. As discussed, the role of autophagy in gastrointestinal diseases is complex and, at times, contentious. To harness the full therapeutic potential of autophagy in treating these conditions, more in-depth research is imperative.

The role of autophagy in pancreatic diseases.

Pancreatic diseases such as pancreatitis and pancreatic cancer represent significant health challenges characterized by high mortality rates and limited survival durations. Autophagy, a crucial cellular catabolic process, has emerged as a focal point in understanding various pathological conditions, spanning inflammation-related disorders to malignant neoplasms. This comprehensive review aims to elucidate the biological intricacies of autophagy and its pivotal roles within two extensively researched pancreatic diseases, namely pancreatitis and pancreatic cancer, drawing upon recent scholarly contributions. The discussion will delve into the nuanced mechanisms underlying autophagy's involvement in these diseases, shedding light on its potential as a therapeutic target. Furthermore, the review will explore cutting-edge therapeutic interventions leveraging autophagy regulation for managing pancreatitis and pancreatic cancer. Through this analysis, we endeavor to offer novel insights into the pathophysiology of pancreatic disorders and contribute to the development of innovative therapeutic modalities in this challenging clinical domain.

Binding Modalities and Phase-Specific Regulation of Cyclin/Cyclin-Dependent Kinase Complexes in the Cell Cycle.

Cyclin-dependent kinases (CDKs) are activated upon cyclin-binding to enable progression through the cell cycle. Dominant CDKs and cyclins in mammalian cells include CDK1, CDK2, CDK4, and CDK6 and corresponding cyclins A, B, D, and E. While only certain, "typical" cyclin/CDK complexes are primarily responsible for cell cycle progression, "atypical" cyclin/CDK complexes can form and sometimes perform the same roles as typical complexes. We asked what structural features of cyclins and CDKs favor the formation of typical complexes, a vital yet not fully explored question. We use computational docking and biophysical analyses to exhaustively evaluate the structure and stability of all CDK and cyclin complexes listed above. We find that binding of the complexes is generally stronger for typical than for atypical complexes, especially when the CDK is in an active conformation. Typical complexes have denser clusters, indicating that they have more defined cyclin-binding sites than atypical complexes. Our results help explain three notable features of cyclin/CDK function in the cell cycle: (i) why CDK4 and cyclin-D have exceptionally high specificity for each other; (ii) why both cyclin-A and cyclin-B strongly activate CDK1, whereas CDK2 is only strongly activated by cyclin-A; and (iii) why cyclin-E normally activates CDK2 but not CDK1. Overall, this work reveals the binding modalities of cyclin/CDK complexes, how the modalities lead to the preference for typical complexes versus atypical complexes, and how binding modalities differ between typical complexes. Our observations suggest targeting CDK catalytic actions through destabilizing their native differential cyclin interfaces.

Genetic Structure and Genome-Wide Association Analysis of Growth and Reproductive Traits in Fengjing Pigs.

The Fengjing pig is one of the local pig breed resources in China and has many excellent germplasm characteristics. However, research on its genome is lacking. To explore the degree of genetic diversity of the Fengjing pig and to deeply explore its excellent traits, this study took Fengjing pigs as the research object and used the Beadchip Array Infinium iSelect-96|XT KPS_PorcineBreedingChipV2 for genotyping. We analyzed the genetic diversity, relatedness, inbreeding coefficient, and population structure within the Fengjing pig population. Our findings revealed that the proportion of polymorphic markers (PN) was 0.469, and the effective population size was 6.8. The observed and expected heterozygosity were 0.301 and 0.287, respectively. The G-matrix results indicated moderate relatedness within the population, with certain individuals exhibiting closer genetic relationships. The NJ evolutionary tree classified Fengjing boars into five family lines. The average inbreeding coefficient based on ROH was 0.318, indicating a high level of inbreeding. GWAS identified twenty SNPs significantly associated with growth traits (WW, 2W, and 4W) and reproductive traits (TNB and AWB). Notably, WNT8B, RAD21, and HAO1 emerged as candidate genes influencing 2W, 4W, and TNB, respectively. Genes such as WNT8B were verified by querying the PigBiobank database. In conclusion, this study provides a foundational reference for the conservation and utilization of Fengjing pig germplasm resources and offers insights for future molecular breeding efforts in Fengjing pigs.

Use of peroral cholangiopancreatoscopy-assisted endoscopic mucosal resection for biliopancreatic intraductal lesions.

BACKGROUND: This study aimed to assess the feasibility and safety of performing cholangiopancreatoscopy-assisted endoscopic mucosal resection (CA-EMR) for biliopancreatic intraductal lesions. METHODS: Special electrocautery snares and injection needles that can pass through the working channel of a single-operator cholangiopancreatoscope were developed. Between November 2023 and April 2024, we performed CA-EMR for two patients with gallbladder polyps, one patient with a neoplastic lesion in the common bile duct (CBD), and one patient with a neoplastic lesion in the main pancreatic duct. The technical success rate and adverse events were recorded. RESULTS: All four CA-EMR procedures were performed successfully. Postoperative pathology revealed inflammatory gallbladder polyps in two patients, low grade intraepithelial neoplasia of the CBD in one patient, and intraductal papillary mucinous neoplasm (IPMN) in one patient. The patient with IPMN experienced mild postoperative pancreatitis and recovered after conservative treatment. No adverse events were encountered in the other three CA-EMR procedures. CONCLUSION: This study preliminarily confirmed the feasibility and safety of CA-EMR for treating biliopancreatic intraductal lesions.

Gender effect in human-machine communication: a neurophysiological study.

Purpose: This study aimed to investigate the neural mechanism by which virtual chatbots' gender might influence users' usage intention and gender differences in human-machine communication. Approach: Event-related potentials (ERPs) and subjective questionnaire methods were used to explore the usage intention of virtual chatbots, and statistical analysis was conducted through repeated measures ANOVA. Results/findings: The findings of ERPs revealed that female virtual chatbots, compared to male virtual chatbots, evoked a larger amplitude of P100 and P200, implying a greater allocation of attentional resources toward female virtual chatbots. Considering participants' gender, the gender factors of virtual chatbots continued to influence N100, P100, and P200. Specifically, among female participants, female virtual chatbots induced a larger P100 and P200 amplitude than male virtual chatbots, indicating that female participants exhibited more attentional resources and positive emotions toward same-gender chatbots. Conversely, among male participants, male virtual chatbots induced a larger N100 amplitude than female virtual chatbots, indicating that male participants allocated more attentional resources toward male virtual chatbots. The results of the subjective questionnaire showed that regardless of participants' gender, users have a larger usage intention toward female virtual chatbots than male virtual chatbots. Value: Our findings could provide designers with neurophysiological insights into designing better virtual chatbots that cater to users' psychological needs.

Mitogen signaling strength and duration can control cell cycle decisions.

Decades ago, mitogen-promoted signaling duration and strength were observed to be sensed by the cell and to be critical for its decisions: to proliferate or differentiate. Landmark publications established the importance of mitogen signaling not only in the G1 cell cycle phase but also through the S and the G2/M transition. Despite these early milestones, how mitogen signal duration and strength, short and strong or weaker and sustained, control cell fate has been largely unheeded. Here, we center on cardinal signaling-related questions, including (i) how fluctuating mitogenic signals are converted into cell proliferation-differentiation decisions and (ii) why extended duration of weak signaling is associated with differentiation, while bursts of strong and short induce proliferation but, if too strong and long, induce irreversible senescence. Our innovative broad outlook harnesses cell biology and protein conformational ensembles, helping us to define signaling strength, clarify cell cycle decisions, and thus cell fate.

CDK2 and CDK4: Cell Cycle Functions Evolve Distinct, Catalysis-Competent Conformations, Offering Drug Targets.

Cyclin-dependent kinases (CDKs), particularly CDK4 and CDK2, are crucial for cell cycle progression from the Gap 1 (G1) to the Synthesis (S) phase by phosphorylating targets such as the Retinoblastoma Protein (Rb). CDK4, paired with cyclin-D, operates in the long G1 phase, while CDK2 with cyclin-E, manages the brief G1-to-S transition, enabling DNA replication. Aberrant CDK signaling leads to uncontrolled cell proliferation, which is a hallmark of cancer. Exactly how they accomplish their catalytic phosphorylation actions with distinct efficiencies poses the fundamental, albeit overlooked question. Here we combined available experimental data and modeling of the active complexes to establish their conformational functional landscapes to explain how the two cyclin/CDK complexes differentially populate their catalytically competent states for cell cycle progression. Our premise is that CDK catalytic efficiencies could be more important for cell cycle progression than the cyclin-CDK biochemical binding specificity and that efficiency is likely the prime determinant of cell cycle progression. We observe that CDK4 is more dynamic than CDK2 in the ATP binding site, the regulatory spine, and the interaction with its cyclin partner. The N-terminus of cyclin-D acts as an allosteric regulator of the activation loop and the ATP-binding site in CDK4. Integrated with a suite of experimental data, we suggest that the CDK4 complex is less capable of remaining in the active catalytically competent conformation, and may have a lower catalytic efficiency than CDK2, befitting their cell cycle time scales, and point to critical residues and motifs that drive their differences. Our mechanistic landscape may apply broadly to kinases, and we propose two drug design strategies: (i) allosteric Inhibition by conformational stabilization for targeting allosteric CDK4 regulation by cyclin-D, and (ii) dynamic entropy-optimized targeting which leverages the dynamic, entropic aspects of CDK4 to optimize drug binding efficacy.

Detection and Analysis of Antidiarrheal Genes and Immune Factors in Various Shanghai Pig Breeds.

The aim of this study was to identify effective genetic markers for the Antigen Processing Associated Transporter 1 (TAP1), α (1,2) Fucosyltransferase 1 (FUT1), Natural Resistance Associated Macrophage Protein 1 (NRAMP1), Mucin 4 (MUC4) and Mucin 13 (MUC13) diarrhea-resistance genes in the local pig breeds, namely Shanghai white pigs, Fengjing pigs, Shawutou pigs, Meishan pigs and Pudong white pigs, to provide a reference for the characterization of local pig breed resources in Shanghai. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLR) and sequence sequencing were applied to analyze the polymorphisms of the above genes and to explore the effects on the immunity of Shanghai local pig breeds in conjunction with some immunity factors. The results showed that both TAP1 and MUC4 genes had antidiarrheal genotype GG in the five pig breeds, AG and GG genotypes of the FUT1 gene were detected in Pudong white pigs, AA antidiarrheal genes of the NRAMP1 gene were detected in Meishan pigs, the AB type of the NRAMP1 gene was detected in Pudong white pigs, and antidiarrheal genotype GG of the MUC13 gene was only detected in Shanghai white pigs. The MUC13 antidiarrhea genotype GG was only detected in Shanghai white pigs. The TAP1 gene was moderately polymorphic in Shanghai white pigs, Fengjing pigs, Shawutou pigs, Meishan pigs and Pudong white pigs, among which TAP1 in Shanghai white pigs and Shawutou pigs did not satisfy the Hardy-Weinberg equilibrium. The FUT1 gene of Pudong white pigs was in a state of low polymorphism. NRAMP1 of Meishan pigs and Pudong white pigs was in a state of moderate polymorphism, which did not satisfy the Hardy-Weinberg equilibrium. The MUC4 genes of Shanghai white pigs and Pudong white pigs were in a state of low polymorphism, and the MUC4 genes of Fengjing pigs and Shawutou pigs were in a state of moderate polymorphism, and the MUC4 genes of Fengjing pigs and Pudong white pigs did not satisfy the Hardy-Weinberg equilibrium. The MUC13 gene of Shanghai white pigs and Pudong white pigs was in a state of moderate polymorphism. Meishan pigs had higher levels of IL-2, IL-10, IgG and TNF-α, and Pudong white pigs had higher levels of IL-12 than the other pigs. The level of interleukin 12 (IL-12) was significantly higher in the AA genotype of the MUC13 gene of Shanghai white pigs than in the AG genotype. The indicator of tumor necrosis factor alpha (TNF-α) in the AA genotype of the TAP1 gene of Fengjing pigs was significantly higher than that of the GG and AG genotypes. The indicator of IL-12 in the AG genotype of the Shawutou pig TAP1 gene was significantly higher than that of the GG genotype. The level of TNF-α in the AA genotype of the NRAMP1 gene of Meishan pigs was markedly higher than that of the AB genotype. The IL-2 level of the AG type of the FUT1 gene was obviously higher than that of the GG type of Pudong white pigs, the IL-2 level of the AA type of the MUC4 gene was dramatically higher than that of the AG type, and the IgG level of the GG type of the MUC13 gene was apparently higher than that of the AG type. The results of this study are of great significance in guiding the antidiarrhea breeding and molecular selection of Shanghai white pigs, Fengjing pigs, Shawutou pigs, Meishan pigs and Pudong white pigs and laying the foundation for future antidiarrhea breeding of various local pig breeds in Shanghai.

Slower CDK4 and faster CDK2 activation in the cell cycle.

Dysregulation of cyclin-dependent kinases (CDKs) impacts cell proliferation, driving cancer. Here, we ask why the cyclin-D/CDK4 complex governs cell cycle progression through the longer G1 phase, whereas cyclin-E/CDK2 regulates the shorter G1/S phase transition. We consider available experimental cellular and structural data including cyclin-E's high-level burst, sustained duration of elevated cyclin-D expression, and explicit solvent molecular dynamics simulations of the inactive monomeric and complexed states, to establish the conformational tendencies along the landscape of the distinct activation scenarios of cyclin-D/CDK4 and cyclin-E/CDK2 in the G1 phase and G1/S transition of the cell cycle, respectively. These lead us to propose slower activation of cyclin-D/CDK4 and rapid activation of cyclin-E/CDK2. We provide the mechanisms through which this occurs, offering innovative CDK4 drug design considerations. Our insightful mechanistic work addresses a compelling cell cycle regulation question and illuminates the distinct activation speeds between the G1 and the G1/S phases, which are crucial for function.

Evaluation of Dry Ice for Short-Term Storage and Transportation of Frozen Boar Semen.

To address the safety problems posed by the transportation of boar semen using LN, this study was conducted on the short-term storage of frozen boar semen in dry ice (-79 °C). Boar semen frozen in LN was transferred to dry ice, kept for 1 day, 3 days, 5 days, 7 days, or 8 days, and then moved back to LN. The quality of frozen semen stored in LN or dry ice was determined to evaluate the feasibility of short-distance transportation with dry ice. The results showed that 60 °C for 8 s was the best condition for thawing frozen semen stored in dry ice. No significant differences in spermatozoa motility, plasma membrane integrity, or acrosome integrity were observed in semen after short-term storage in dry ice compared to LN (p > 0.05). There were no significant changes in antioxidant properties between storage groups either (p > 0.05). In conclusion, dry ice could be used as a cold source for the short-term transportation of frozen boar semen for at least 7 days, without affecting sperm motility, morphological integrity, or antioxidant indices.

Computer-aided diagnosis system for optical diagnosis of colorectal polyps under white light imaging.

OBJECTIVES: This study presents a novel computer-aided diagnosis (CADx) designed for optically diagnosing colorectal polyps using white light imaging (WLI).We aimed to evaluate the effectiveness of the CADx and its auxiliary role among endoscopists with different levels of expertise. METHODS: We collected 2,324 neoplastic and 3,735 nonneoplastic polyp WLI images for model training, and 838 colorectal polyp images from 740 patients for model validation. We compared the diagnostic accuracy of the CADx with that of 15 endoscopists under WLI and narrow band imaging (NBI). The auxiliary benefits of CADx for endoscopists of different experience levels and for identifying different types of colorectal polyps was also evaluated. RESULTS: The CADx demonstrated an optical diagnostic accuracy of 84.49%, showing considerable superiority over all endoscopists, irrespective of whether WLI or NBI was used (P < 0.001). Assistance from the CADx significantly improved the diagnostic accuracy of the endoscopists from 68.84% to 77.49% (P = 0.001), with the most significant impact observed among novice endoscopists. Notably, novices using CADx-assisted WLI outperform junior and expert endoscopists without such assistance. CONCLUSIONS: The CADx demonstrated a crucial role in substantially enhancing the precision of optical diagnosis for colorectal polyps under WLI and showed the greatest auxiliary benefits for novice endoscopists.

The role of C18 fatty acids in improving the digestion and retrogradation properties of highland barley starch.

In this study, five C18 fatty acids (FA) with different numbers of double bonds and configurations including stearic acid (SA), oleic acid (OA), elaidic acid (EA), linoleic acid (LA), and α-linolenic acid (ALA), were selected to prepare highland barely starch (HBS)-FA complexes to modulate digestibility and elaborate the underlying mechanism. The results showed that HBS-SA had the highest complex index (34.18 %), relative crystallinity (17.62 %) and single helix content (25.78 %). Furthermore, the HBS-C18 FA complexes were formed by EA (C18 FA with monounsaturated bonds) that had the highest R1047/1022 (1.0509) and lowest full width at half-maximum (FWHM, 20.85), suggesting good short-range ordered structure. Moreover, all C18 FAs could form two kinds of V-type complexes with HBS, which can be confirmed by the results of CLSM and DSC measurements, and all of them showed significantly lower digestibility. HBS-EA possessed the highest resistant starch content (20.17 %), while HBS-SA had the highest slowly digestible starch content (26.61 %). In addition, the inhibition of HBS retrogradation by fatty acid addition was further proven, where HBS-SA gel firmness (37.80 g) and aging enthalpy value were the lowest, indicating the most effective. Overall, compounding with fatty acids, especially SA, could be used as a novel way to make functional foods based on HBS.

Metabolomics Characterization of Phenolic Compounds in Colored Quinoa and Their Relationship with In Vitro Antioxidant and Hypoglycemic Activities.

Chenopodium quinoa Willd. is rich in phenolic compounds and exhibits diverse biological activities. Few studies have focused on the effect of colored quinoa's phenolic profile on potential biological activity. This study used a UPLC-MS/MS-based metabolomic approach to examine the quinoa phenolics and their association with in vitro antioxidant and hypoglycemic properties. In total, 430 polyphenols, mainly phenolic acids, flavonoids, and flavonols, were identified. Additionally, 121, 116, and 148 differential polyphenols were found between the white and black, white and red, and black and red comparison groups, respectively; 67 polyphenols were screened as shared key differential metabolites. Phenylalanine, tyrosine, and the biosynthesis of plant secondary metabolites were the main differently regulated pathways. Black quinoa had better total phenolic contents (643.68 mg/100 g DW) and antioxidant capacity, while white quinoa had better total flavonoid contents (90.95 mg/100 g DW) and in vitro α-amylase (IC50 value of 3.97 mg/mL) and α-glucosidase (IC50 value of 1.08 mg/mL) inhibition activities. Thirty-six polyphenols, including epicatechin and linarin, etc., were highly correlated with in vitro antioxidant activity, while six polyphenols, including tiliroside and chrysoeriol, etc., were highly correlated with in vitro hypoglycemic activity. This study may provide important information for colored quinoa resources to develop their healthy food applications.

How does proactive personality affect employee creativity and ostracism? The mediating role of envy.

When working alongside proactive colleagues, do you elevate yourself through benign envy or resort to malicious envy? To address this intriguing question, we constructed a model based on social comparison theory to measure the double-edged sword effects of proactive personality on employee outcomes. We hypothesized that proactive employees would induce two distinct tendencies in their peers-workplace ostracism and employee creativity-due to peer envy. The study analyzed 389 valid responses from full-time employees in Chinese organizations using structural equation modeling. Results indicate that proactive personality positively influences benign envy among peers, which in turn positively affects employee creativity. Moreover, benign envy mediates the relationship between proactive personality and employee creativity. On the other hand, proactive personality positively influences malicious envy among peers, which in turn positively affects workplace ostracism. Additionally, malicious envy mediates the relationship between proactive personality and workplace ostracism. This study intertwines personality, emotions, and workplace outcomes, thereby advancing the existing literature on social comparison theory. Additionally, it furnishes valuable insights for organizational human resource management, particularly in the realms of employee recruitment and workplace relationship management.

An investigation into the effects of various processing methods on the characteristic compounds of highland barley using a widely targeted metabolomics approach.

This study explored the influence of diverse processing methods (cooking (CO), extrusion puffing (EX), and steam explosion puffing (SE), stir-frying (SF) and fermentation (FE)) on highland barley (Qingke) chemical composition using UHPLC-MS/MS based widely targeted metabolomics. Overall, 827 metabolites were identified and categorized into 16 classes, encompassing secondary metabolites, amino acids, nucleotides, lipids, etc. There 43, 85, 131, 51 and 98 differential metabolites were respectively selected from five comparative groups (raw materials (RM) vs CO/EX/SE/SF/FE), mainly involved in amino acids, nucleotides, flavonoids, and alkaloids. Compared to other treated groups, FE group possessed the higher content of crude protein (15.12 g/100 g DW), and the relative levels of free amino acids (1.32 %), key polyphenols and arachidonic acid (0.01 %). EX group had the higher content of anthocyanins (4.22 mg/100 g DW), and the relative levels of free amino acids (2.02 %) and key polyphenols. SE group showed the higher relative levels of phenolic acids (0.14 %), flavonoids (0.20 %) and alkaloids (1.17 %), but the lowest free amino acids (0.75 %). Different processing methods all decreased Qingke's antioxidant capacity, with the iron reduction capacity (988.93 µmol/100 g DW) in SE group was the lowest. On the whole, FE and EX were alleged in improving Qingke's nutritional value. CO and SF were also suitable for Qingke processing since fewer differential metabolites were identified in CO vs RM and SF vs RM groups. Differential metabolites were connected to 14 metabolic pathways, with alanine, aspartate, and glutamate metabolism being central. This study contributed theoretical groundwork for the scientific processing and quality control of Qingke products.

Change of physiochemical characteristics, nutritional quality, and volatile compounds of Chenopodium quinoa Willd. during germination.

The impacts of varying germination periods (0-72 h) on morphological properties, proximate composition, amino acid profile, GABA levels, antioxidant attributes, polyphenol content (both free and bound), and volatile compounds of quinoa were evaluated. Germination significantly increased the content of fiber, amino acids, GABA, polyphenols, and in-vitro antioxidant activities in quinoa. The optimal nutritional quality and antioxidant capacity of quinoa were observed during the 36-72 h germination period. We examined the dynamics of 47 phenolic compounds in quinoa during germination and noted a substantial rise in free phenolic acids and bound flavonoids post-germination. A total of 53 and 84 volatile compounds were respectively identified in ungerminated quinoa and germinated quinoa. It was found that the germination period of 24-48 h contributed to reducing the presence of undesirable flavors. TEM analysis revealed significant structural damage to the ultrastructure and relaxation of the cell wall in germinated quinoa grains.