Moonlighting glyceraldehyde-3-phosphate dehydrogenase of Lactobacillus gasseri inhibits keratinocyte apoptosis and skin inflammation in experimental atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. OBJECTIVE: Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. METHODS: In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. RESULTS: L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. CONCLUSION: The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

Probing the Surface Layer Modulation on Archaeal Mechanics and Adhesion at the Single-Cell Level.

Addressing the challenge of understanding how cellular interfaces dictate the mechanical resilience and adhesion of archaeal cells, this study demonstrates the role of the surface layer (S-layer) in methanogenic archaea. Using a combination of atomic force microscopy and single-cell force spectroscopy, we quantified the impact of S-layer disruption on cell morphology, mechanical properties, and adhesion capabilities. We demonstrate that the S-layer is crucial for maintaining cell morphology, where its removal induces significant cellular enlargement and deformation. Mechanical stability of the cell surface is substantially compromised upon S-layer disruption, as evidenced by decreased Young's modulus values. Adhesion experiments revealed that the S-layer primarily facilitates hydrophobic interactions, which are significantly reduced after its removal, affecting both cell-cell and cell-bubble interactions. Our findings illuminate the S-layer's fundamental role in methanogen architecture and provide a chemical understanding of archaeal cell surfaces, with implications for enhancing methane production in biotechnological applications.

Uncommon Epoxyquinols Pyrrolocytosporin A and cytosporin E2from the Fungus Eutypella sp. D-1.

Two uncommon epoxyquinols, pyrrolocytosporin A (1) and cytosporin E2 (2), along with the known cytosporin Y1 (3), were isolated from the solid defined medium of the Arctic-derived fungus Eutypella sp. D-1. Their structures were established through comprehensive analyses of spectroscopic and electronic circular dichroism data. Structurally, compound 1 represented the first nitrogen-containing epoxyquinol characterized by a pyrrole fused cytosporin framework, while compound 2 contained an uncommon cyclic carbonate functionality. The antibacterial, immunosuppressive, anti-inflammatory, and cytotoxic activities of all compounds were evaluated. Among the three metabolites, only compound 1 exhibited inhibitory effects on nitric oxide production induced by lipopolysaccharide with an IC50 value of 6.55 µM. Additionally, only compound 2 displayed inhibitory activity against ConA-induced T-cell proliferation with an IC50 value of 9.85 µM.

Early postoperative complications after transverse colostomy closure, a retrospective study.

BACKGROUND: Ostomy is a common surgery usually performed to protect patients from clinical symptoms caused by distal anastomotic leakage after colorectal cancer (CRC) surgery and perforation or to relieve intestinal obstruction. AIM: To analyze the complications after transverse colostomy closure. METHODS: Patients who underwent transverse colostomy closure from Jan 2015 to Jan 2022 were retrospectively enrolled in a single clinical center. The differences between the complication group and the no complication group were compared. Logistic regression analyses were conducted to find independent factors for overall complications or incision infection. RESULTS: A total of 102 patients who underwent transverse colostomy closure were enrolled in the current study. Seventy (68.6%) patients underwent transverse colostomy because of CRC related causes. Postoperative complications occurred in 30 (29.4%) patients and the most frequent complication occurring after transverse colostomy closure was incision infection (46.7%). The complication group had longer hospital stays (P < 0.01). However, no potential risk factors were identified for overall complications and incision infection. CONCLUSION: The most frequent complication occurring after transverse colostomy closure surgery in our center was incision infection. The operation time, interval from transverse colostomy to reversal, and method of anastomosis might have no impact on the postoperative complications. Surgeons should pay more attention to aseptic techniques.

The effect of feeding on different hosts on the egg proteins in Haemaphysalis qinghaiensis tick.

The majority of ixodid ticks display host-specificity to varying extents. Feeding on different hosts affects their development and reproduction. Consequences can be analyzed at the level of the egg, as it is the initial stage of tick development. Tick egg proteins are abundant and diverse, providing nutrients for embryonic development. However, studies on tick egg profiles are scarce. In this study, we aimed to analyze whether feeding Haemaphysalis qinghaiensis ticks on the yaks (Bos grunniens) and domestic sheep (Ovis aries) has an impact on the variety and variability of the egg proteome. Detached engorged females were used to lay eggs, which were then collected, dewaxed, and subjected to protein extraction. The extracted egg proteins were enzymatically digested using Filter-Aided Sample Preparation (FASP), and the unique peptides were separated and detected by Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS). The MS data were searched against the previously constructed whole tick transcriptome library of H. qinghaiensis, and the UniProt database for the identification of tick-derived egg proteins. The analysis revealed 49 and 53 high-confidence proteins identified in eggs collected from B. grunniens (EggBg) and O. aries (EggOa), respectively. Of these, 46 high-confidence proteins were common to both egg types, while three were unique to EggBg and seven to EggOa. All the identified proteins mainly belonged to enzymes, enzyme inhibitors, transporters, and proteins with unknown functions. The differential abundance analysis showed that nine proteins were significantly more present in EggBg, while six were significantly more present in EggOa. Overall, enzymes were the most diverse group, while vitellogenin (Vg) was the most abundant. Blood meal uptake on different hosts has a certain effect on the egg proteome composition and the abundance of some proteins, but it may also lead to compensation of protein roles.

Is recovery enhancement after gastric cancer surgery really a safe approach for elderly patients?

BACKGROUND: This study aimed to evaluate the safety of enhanced recovery after surgery (ERAS) in elderly patients with gastric cancer (GC). AIM: To evaluate the safety of ERAS in elderly patients with GC. METHODS: The PubMed, EMBASE, and Cochrane Library databases were used to search for eligible studies from inception to April 1, 2023. The mean difference (MD), odds ratio (OR) and 95% confidence interval (95%CI) were pooled for analysis. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale scores. We used Stata (V.16.0) software for data analysis. RESULTS: This study consists of six studies involving 878 elderly patients. By analyzing the clinical outcomes, we found that the ERAS group had shorter postoperative hospital stays (MD = -0.51, I2 = 0.00%, 95%CI = -0.72 to -0.30, P = 0.00); earlier times to first flatus (defecation; MD = -0.30, I² = 0.00%, 95%CI = -0.55 to -0.06, P = 0.02); less intestinal obstruction (OR = 3.24, I2 = 0.00%, 95%CI = 1.07 to 9.78, P = 0.04); less nausea and vomiting (OR = 4.07, I2 = 0.00%, 95%CI = 1.29 to 12.84, P = 0.02); and less gastric retention (OR = 5.69, I2 = 2.46%, 95%CI = 2.00 to 16.20, P = 0.00). Our results showed that the conventional group had a greater mortality rate than the ERAS group (OR = 0.24, I2 = 0.00%, 95%CI = 0.07 to 0.84, P = 0.03). However, there was no statistically significant difference in major complications between the ERAS group and the conventional group (OR = 0.67, I2 = 0.00%, 95%CI = 0.38 to 1.18, P = 0.16). CONCLUSION: Compared to those with conventional recovery, elderly GC patients who received the ERAS protocol after surgery had a lower risk of mortality.

Design, synthesis, and evaluation of novel ferrostatin derivatives for the prevention of HG-induced VEC ferroptosis.

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

Nitrogen Forms Regulate the Response of Microcystis aeruginosa to Nanoplastics at Environmentally Relevant Nitrogen Concentrations.

As essential primary producers, cyanobacteria play a major role in global carbon and nitrogen cycles. Though the influence of nanoplastics on the carbon metabolism of cyanobacteria is well-studied, little is known about how nanoplastics affect their nitrogen metabolism, especially under environmentally relevant nitrogen concentrations. Here, we show that nitrogen forms regulated growth inhibition, nitrogen consumption, and the synthesis and release of microcystin (MC) in Microcystis aeruginosa exposed to 10 µg/mL amino-modified polystyrene nanoplastics (PS-NH2) with a particle size of 50 nm under environmentally relevant nitrogen concentrations of nitrate, ammonium, and urea. We demonstrate that PS-NH2 inhibit M. aeruginosa differently in nitrate, urea, and ammonium, with inhibition rates of 51.87, 39.70, and 36.69%, respectively. It is caused through the differences in impairing cell membrane integrity, disrupting redox homeostasis, and varying nitrogen transport pathways under different nitrogen forms. M. aeruginosa respond to exposure of PS-NH2 by utilizing additional nitrogen to boost the production of amino acids, thereby enhancing the synthesis of MC, extracellular polymeric substances, and membrane phospholipids. Our results found that the threat of nanoplastics on primary producers can be regulated by the nitrogen forms in freshwater ecosystems, contributing to a better understanding of nanoplastic risks under environmentally relevant conditions.

Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system.

Silent information regulator 2 (Sir2) proteins typically catalyze NAD+-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD+ to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2-DSAD1 and DSR2-DSAD1-NAD+, as well as active DSR2-tube and DSR2-tube-NAD+ complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTDclosed or CTDopen. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTDclosed and activate Sir2 for NAD+ hydrolysis. DSAD1 binding to CTDopen allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD+ substrate catalysis in bacterial DSR2 anti-phage defense systems.

Observation of D-class topology in an acoustic metamaterial.

Topological materials and metamaterials opened new paradigms to create and manipulate phases of matter with unconventional properties. Topological D-class phases (TDPs) are archetypes of the ten-fold classification of topological phases with particle-hole symmetry. In two dimensions, TDPs support propagating topological edge modes that simulate the elusive Majorana elementary particles. Furthermore, a piercing of π-flux Dirac-solenoids in TDPs stabilizes localized Majorana excitations that can be braided for the purpose of topological quantum computation. Such two-dimensional (2D) TDPs have been a focus in the research frontier, but their experimental realizations are still under debate. Here, with a novel design scheme, we realize 2D TDPs in an acoustic crystal by synthesizing both the particle-hole and fermion-like time reversal symmetries for a wide range of frequencies. The design scheme leverages an enriched unit cell structure with real-valued couplings that emulate the targeted Hamiltonian of TDPs with complex hoppings: A technique that could unlock the realization of all topological classes with passive metamaterials. In our experiments, we realize a pair of TDPs with opposite Chern numbers in two independent sectors that are connected by an intrinsic fermion-like time-reversal symmetry built in the system. We measure the acoustic Majorana-like helical edge modes and visualize their robust topological transport, thus revealing the unprecedented D and DIII class topologies with direct evidence. Our study opens up a new pathway for the experimental realization of two fundamental classes of topological phases and may offer new insights in fundamental physics, materials science, and phononic information processing.

Asymmetric Synthesis of the Functionalized A/E-Ring Fragment of C18-Diterpenoid Alkaloids.

A new asymmetric synthesis of the A/E-ring fragment of C18-diterpenoid alkaloids is described. The crucial contiguous stereogenic centers at C4, C5, and C11 were established through an asymmetric Michael addition/allylation sequence. The unique azabicyclo[3.3.1]nonane motif (A/E rings) was assembled by employing ring-closing metathesis and Mitsunobu reaction as key strategies.

Exploring the causal factor effects of hypothyroidism on ischemic stroke: a two-sample Mendelian randomization study.

Background: Observational studies have suggested a possible association between hypothyroidism and increased risk of ischemic stroke. However, a causal relationship remains unclear. Methods: Data on single nucleotide polymorphisms (SNPs) associated with hypothyroidism and ischemic stroke were sourced from the FinnGens database and the UK Biobank of European descent. Both databases underwent separate two-sample Mendelian randomization (MR) analyses. A subsequent meta-analysis of MR results using a random-effects model was conducted to determine the causal relationship between hypothyroidism and ischemic stroke. Results: All five analyses indicated a positive causal relationship between hypothyroidism and ischemic stroke. MR analysis of the association between hypothyroidism and ischemic stroke yielded a result of the inverse variance weighted (IVW) method at 4.7411 (1.3598-16.5308), p = 0.0146. The analysis of ischemic stroke (without excluding controls) yielded a result of the IVW method of 4.5713 (1.3570-15.3986), p = 0.0142. MR analysis with cerebral infarction yielded a result of the IVW method at 1.0110 (1.0006-1.0215), p = 0.0373. The MR analysis with cerebrovascular disease sequelae yielded an IVW method result of 2.4556 (1.0291-5.8595), p = 0.0429. Analysis for the sequelae of cerebrovascular disease (without excluding controls) yielded an IVW method result of 2.4217 (1.0217-5.7402), p = 0.0446. No evidence of heterogeneity or horizontal pleiotropy was found. The meta-analysis of the five MR results was 2.24 (1.18-4.26), p = 0.025. Conclusion: Our two-sample Mendelian randomization study suggested a causal relationship between hypothyroidism and ischemic stroke, indicating that hypothyroidism could be a risk factor for ischemic stroke. However, further studies are required to elucidate the underlying biological mechanisms.

Eutypellaolides A-J, Sesquiterpene diversity expansion of the polar fungus Eutypella sp. D-1.

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A-H (1-8), and two new eudesmane-type sesquiterpenes, eutypellaolides I-J (9-10), along with four known 12,8-eudesmanolide compounds 11-14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 µg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 µM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 µM, respectively.

Measuring entanglement entropy and its topological signature for phononic systems.

Entanglement entropy is a fundamental concept with rising importance in various fields ranging from quantum information science, black holes to materials science. In complex materials and systems, entanglement entropy provides insight into the collective degrees of freedom that underlie the systems' complex behaviours. As well-known predictions, the entanglement entropy exhibits area laws for systems with gapped excitations, whereas it follows the Gioev-Klich-Widom scaling law in gapless fermion systems. However, many of these fundamental predictions have not yet been confirmed in experiments due to the difficulties in measuring entanglement entropy in physical systems. Here, we report the experimental verification of the above predictions by probing the nonlocal correlations in phononic systems. We obtain the entanglement entropy and entanglement spectrum for phononic systems with the fermion filling analog. With these measurements, we verify the Gioev-Klich-Widom scaling law. We further observe the salient signatures of topological phases in entanglement entropy and entanglement spectrum.

Heterotopic mineralization (ossification or calcification) in aged musculoskeletal soft tissues: A new candidate marker for aging.

Aging can lead to various disorders in organisms and with the escalating impact of population aging, the incidence of age-related diseases is steadily increasing. As a major risk factor for chronic illnesses in humans, the prevention and postponement of aging have become focal points of research among numerous scientists. Aging biomarkers, which mirror molecular alterations at diverse levels in organs, tissues, and cells, can be used to monitor and evaluate biological changes associated with aging. Currently, aging biomarkers are primarily categorized into physiological traits, imaging characteristics, histological features, cellular-level alterations, and molecular-level changes that encompass the secretion of aging-related factors. However, in the context of the musculoskeletal soft tissue system, aging-related biological indicators primarily involve microscopic parameters at the cellular and molecular levels, resulting in inconvenience and uncertainty in the assessment of musculoskeletal soft tissue aging. To identify convenient and effective indicators, we conducted a comprehensive literature review to investigate the correlation between ectopic mineralization and age-related changes in the musculoskeletal soft tissue system. Here, we introduce the concept of ectopic mineralization as a macroscopic, reliable, and convenient biomarker for musculoskeletal soft tissue aging and present novel targets and strategies for the future management of age-related musculoskeletal soft tissue disorders.

Remission of Nonalcoholic Fatty Liver Disease After Radical Surgery in Patients with Colorectal Cancer: A Single-Center Retrospective Study.

Purpose: The purpose of this study was to investigate the relationship between remission of nonalcoholic fatty liver disease (NAFLD) and radical surgery for colorectal cancer (CRC) patients. Methods: From January 2014 to December 2021, data of patients with concurrent CRC and NAFLD who underwent radical surgery in a single-center hospital were retrospectively collected. NAFLD was defined as a mean computed tomography (CT) liver attenuation value of <40 Hounsfield units (HUs). Comparison of preoperative and 1-year postoperative CT images was performed to evaluate the change of NAFLD. Multivariate logistic regression analysis was performed to identify independent predictive factors for NAFLD remission. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS) between the remission group and no remission group. Results: In this study, a total of 55 eligible patients were included. The remission group had 33 (60.0%) patients and the no remission group had 22 (40.0%) patients. The mean preoperative weight was 66.1 ± 9.9 kg. The mean preoperative body mass index (BMI) was 25.4 ± 2.5 kg/m2. We found that the average weight was significantly decreased (P < 0.01), average BMI was significantly decreased (P < 0.01), and HU score was significantly increased (P < 0.01). By comparing baseline characteristics between the remission group and no remission group, we found that the remission group exhibited larger tumor sizes (P = 0.036) than the no remission group. In the multivariate logistic regression analysis, we found that weight change was a predictor for NAFLD (odds ratio = 0.764, 95% confidence interval = 0.618-0.944, P = 0.013). We did not find any statistically significant differences in OS (P = 0.182) or DFS (P = 0.248) between the remission group and no remission group. Conclusions: The NAFLD remission rate reached 60.0% for CRC patients 1 year after radical surgery. In addition, we found that weight change was a predictor of NAFLD remission.

Effect of intraoperative blood loss on postoperative complications and prognosis of patients with colorectal cancer: A meta­analysis.

The purpose of the present study was to evaluate whether the amount of intraoperative blood loss (IBL) affects the complications and prognosis of patients with colorectal cancer (CRC). The PubMed, EMBASE and the Cochrane Library databases were used to search for eligible studies from inception to November 30, 2020. Hazard ratios (HRs) and 95% confidence intervals (Cls) were pooled up. The overall survival (OS) and disease-free survival (DFS) were compared between the larger IBL group and the smaller IBL group. The present study was performed with RevMan 5.3 (The Cochrane Collaboration). A total of seven studies involving 1,540 patients with CRC were included in the present study. The smaller IBL group had a higher rate of OS (HR=1.45, 95% CI=1.17 to 1.8, P=0.0007) and a higher rate of DFS (HR=1.76, 95% CI=1.40 to 2.21, P<0.00001). Furthermore, the larger IBL group had a higher rate of postoperative complications than the smaller IBL group (odds ratio=2.06, 95% CI=1.72 to 2.15, P<0.00001). In conclusion, a smaller IBL was associated with better OS and DFS, and a lower risk of postoperative complications compared with a larger IBL in patients with CRC, suggesting that surgeons should pay more attention during perioperative management and surgical operation to reduce IBL.