Robust topological insulating property in C2X-functionalized III-V monolayers.

Two-dimensional topological insulators (TIs) show great potential applications in low-power quantum computing and spintronics due to the spin-polarized gapless edge states. However, the small bandgap limits their room-temperature applications. Based on first-principles calculations, a series of C2X (X = H, F, Cl, Br and I) functionalized III-V monolayers are investigated. The nontrivial bandgaps of GaBi-(C2X)2, InBi-(C2X)2, TlBi-(C2X)2and TlSb-(C2X)2are found to between 0.223 and 0.807 eV. For GaBi-(C2X)2and InBi-(C2X)2, the topological insulating properties originate from thes-px,yband inversion induced by the spin-orbital coupling (SOC) effect. While for TlBi-(C2X)2and TlSb-(C2X)2, the topological insulating properties are attributed to the SOC effect-induced band splitting. The robust topological characteristics are further confirmed by topological invariantsZ2and the test under biaxial strain. Finally, two ideal substrates are predicted to promote the applications of these TIs. These findings indicate that GaBi-(C2X)2, InBi-(C2X)2, TlBi-(C2X)2and TlSb-(C2X)2monolayers are good candidates for the fabrication of spintronic devices.

The Impact of Oxygen Content in O-Doped MoS2 on the Kinetics of Polysulfide Conversion in Li-S Batteries.

Polysulfide shuttle and sluggish sulfur redox kinetics remain key challenges in lithium-sulfur batteries. Previous researches have shown that introducing oxygen into transition metal sulfides helps to capture polysulfides and enhance their conversion kinetics. Based on this, further investigations are conducted to explore the impact of oxygen doping levels on the physical-chemical properties and electrocatalytic performance of MoS2. The findings reveal that MoS2 doped with high-content oxygen exhibits enhanced conductivity and polysulfides conversion kinetics compared to MoS2 with low-content oxygen doping, which can be attributed to the alteration of crystal structure from 2H-phase to the 1T-phase, the introduction of increased Li-O interactions, and the effect of defects resulting from high-oxygen doping. Consequently, the lithium-sulfur batteries using high-oxygen doped MoS2 as a catalyst deliver a high discharge capacity of 1015 mAh g-1 at 0.25C and maintain 78.5% capacity after 300 more cycles. Specifically, lithium-sulfur batteries employing paper-based electrodedemonstrate an areal capacity of 3.91 mAh cm-2 at 0.15C, even with sulfur loading of 4.1 mg cm-2 and electrolyte of 6.7 µL mg-1. These results indicate that oxygen doping levels can modify the properties of MoS2, and high-oxygen doped MoS2 shows promise as an efficient catalyst for lithium-sulfur batteries.

High-pressure effects on the electronic properties and photoluminescence of Ag-doped CsCu2I3.

CsCu2I3 is a popular lead-free metal halide perovskite with good thermal and air stability. To facilitate its applications in optoelectronics, Ag doping and high pressure are employed in this work to improve the optoelectronic properties of CsCu2I3. Using first-principles calculations and experiments, the structural phase change of 10% Ag-doped CsCu2I3 is found to occur at about 4.0 GPa. This reveals the regulation of band structures by hydrostatic pressure. In addition, the high pressure not only increases the emission energy of photoluminescence of 10% Ag-doped CsCu2I3 by more than 0.2 eV, but also increases the emission intensity by multiple times. Finally, the origin of luminescence in 10% Ag-doped CsCu2I3 is attributed to the I vacancies. This work provides insight into the structure and optoelectronic properties of 10% Ag-doped CsCu2I3, and offers significant guidance for the design and manufacturing of future luminescence devices.

Potential impact of climate change on the distribution of Capricornis milneedwardsii, a vulnerable mammal in China.

Climate change significantly impacted on the survival, development, distribution, and abundance of living organisms. The Chinese serow Capricornis milneedwardsii, known as the "four unlike," is a Class II nationally protected species in China. In this study, we predicted the geographical suitability of C. milneedwardsii under current and future climatic conditions using MaxEnt. The model simulations resulted in area under the receiver operating characteristic curve (AUC) values above 0.9 for both current and future climate scenarios, indicating the excellent performance, high accuracy, and credibility of the MaxEnt model. The results also showed that annual precipitation (Bio12), slope, elevation, and mean temperature of wettest quarter (Bio8) were the key environmental variables affecting the distribution of C. milneedwardsii, with contributions of 31.2%, 26.4%, 11%, and 10.3%, respectively. The moderately and highly suitable habitats were mainly located in the moist area of China, with a total area of 34.56 × 104 and 16.61 × 104 km2, respectively. Under future climate change scenarios, the areas of suitability of C. milneedwardsii showed an increasing trend. The geometric center of the total suitable habitats of C. milneedwardsii would show the trend of northwest expansion and southeast contraction. These findings could provide a theoretical reference for the protection of C. milneedwardsii in the future.

Assessment of the antimicrobial and immunomodulatory activity of QS-CATH, a promising therapeutic agent isolated from the Chinese spiny frogs (Quasipaa spinosa).

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.

Analysis of Distribution and Drug Susceptibility Test Results of Pathogenic Bacteria in Diabetic Foot Ulcers.

INTRODUCTION: This study aimed to determine the pathogen distribution and drug susceptibility of diabetic foot wound secretions in a tertiary hospital in a coastal area of southeastern China to guide clinical antibiotic selection. METHODS: A retrospective analysis was conducted on 212 patients with diabetic foot hospitalized at Xiamen Third Hospital from 2018 to 2023, and foot wound secretions were collected for microbial culture and drug susceptibility testing. RESULTS: Among 212 cases of patients with diabetic foot wound secretions, 163 cases (76.9%) were cultured with pathogenic bacteria, and a total of 207 strains of pathogenic bacteria were cultured, including 75 strains (36.23%) of Gram-positive (G+) bacteria, 118 strains of Gram-negative (G-) bacteria (57.00%), 14 strains of fungi (6.76%), 120 cases of single microorganism infection (73.62%), 43 cases of mixed infection (26.38%), and 15 strains of multidrug-resistant bacteria (7.25%). The top three pathogenic bacteria were Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. G+ bacteria were dominated by S. aureus. Drug susceptibility results showed that G+ bacteria were highly susceptible to vancomycin, linezolid, tigecycline, quinupristin/dalfopristin, rifampicin, and furotoxin, and somewhat resistant to penicillin, erythromycin, clindamycin, and cefoxitin. Among G- bacterial infections, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Proteus were the major species. Drug susceptibility testing indicated that carbapenems such as imipenem and ertapenem were the most effective antibacterial drugs against G- strains, followed by amikacin, piperacillin, and tazabactams to which these bacteria were also relatively sensitive, while resistance to penicillins and first-generation cephalosporins increased significantly. We isolated one strain of pathogenic bacteria from a Wagner grade 1 ulcer, which was G+ bacteria. In Wagner grade 2 ulcers, the distribution of pathogenic bacteria was mainly G+ bacteria. In Wagner grade 3 and 4 ulcers, the distribution of pathogenic bacteria was mainly G- bacteria, and the increased rate of mixed infection was mainly due to mixed infection of G+ and G-. Two strains of pathogenic bacteria were isolated at Wagner grade 5, which were mixed infections of G+ and G-. CONCLUSIONS: Pathogenic bacteria in diabetic foot wounds are predominantly G- bacteria, followed by G+ bacteria. As the Wagner ulcer grade increases, the distribution of pathogenic bacteria changes from G+ bacteria to G- bacteria, and the mixed infection rate increases. G+ bacteria are highly susceptible to vancomycin, linezolid, tigecycline, quinupristin/dalfopristin, rifampicin, and furotoxin, and somewhat resistant to penicillin, erythromycin, clindamycin, and cefoxitin. G- bacteria are more sensitive to the antimicrobial drugs ertapenem, imipenem, amikacin, piperacillin tazobactam, and have high resistance to penicillin and first-generation cephalosporins.

An esculentin-1 homolog from a dark-spotted frog (Pelophylax nigromaculatus) possesses antibacterial and immunoregulatory properties.

BACKGROUND: Esculentin-1, initially discovered in the skin secretions of pool frogs (Pelophylax lessonae), has demonstrated broad-spectrum antimicrobial activity; however, its immunomodulatory properties have received little attention. RESULTS: In the present study, esculentin-1 cDNA was identified by analysing the skin transcriptome of the dark-spotted frog (Pelophylax nigromaculatus). Esculentin-1 from this species (esculentin-1PN) encompasses a signal peptide, an acidic spacer peptide, and a mature peptide. Sequence alignments with other amphibian esculentins-1 demonstrated conservation of the peptide, and phylogenetic tree analysis revealed its closest genetic affinity to esculentin-1P, derived from the Fukien gold-striped pond frog (Pelophylax fukienensis). Esculentin-1PN transcripts were observed in various tissues, with the skin exhibiting the highest mRNA levels. Synthetic esculentin-1PN demonstrated antibacterial activity against various pathogens, and esculentin-1PN exhibited bactericidal activity by disrupting cell membrane integrity and hydrolyzing genomic DNA. Esculentin-1PN did not stimulate chemotaxis in RAW264.7, a murine leukemic monocyte/macrophage cell line. However, it amplified the respiratory burst and augmented the pro-inflammatory cytokine gene (TNF-α and IL-1ß) expression in RAW264.7 cells. CONCLUSIONS: This novel finding highlights the immunomodulatory activity of esculentin-1PN on immune cells.

Targeted cultivation of diatoms in mariculture wastewater by nutrient regulation and UV-C irradiation.

Mariculture wastewater poses environmental challenges due to pollution and eutrophication. Targeted cultivation of diatoms in wastewater can help alleviate these issues while generating beneficial algae biomass, however reliable operating methods are lacking. We proposed a novel method for treating mariculture wastewater that employed UV-C irradiation and nutrient regulation to achieve targeted diatom cultivation. This study first examined growth of four diatom species (Nitzschia closterium, Chaetoceros muelleri, Cyclotella atomus, and Conticribra weissflogii) in mariculture wastewater. C. muelleri and C. weissflogii demonstrated better adaptability compared to N. closterium and C. atomus. Additionally, the growth and nutrient utilization of C. muelleri were studied under varying concentrations of silicate, phosphate, ammonium, and trace elements in wastewater. Optimal growth was observed at 500 µmol/L silicate, 0.6 mg/L phosphate, and 4 mg/L ammonium. Ammonium proved to be a more effective nitrogen source than urea and nitrate in promoting growth at this low level. Surprisingly, trace element supplementation did not significantly impact growth. Finally, this study utilized UV-C irradiation as a pre-treatment method for wastewater prior to nutrient adjustment, significantly enhancing the growth of C. muelleri. Overall, this study provides guidance on regulating key nutrients and pre-treatment method to optimize diatom biomass production from mariculture wastewater. This approach not only addresses environmental challenges associated with mariculture but also contributes to sustainable aquaculture practices through the recovery of valuable aquatic resources.

Genomic and Proteomic Analyses of Extracellular Products Reveal Major Virulence Factors Likely Accounting for Differences in Pathogenicity to Bivalves between Vibrio mediterranei Strains.

Vibrio mediterranei, a bacterial pathogen of bivalves, has exhibited strain-dependent virulence. The mechanisms behind the variations in bivalve pathogenicity between V. mediterranei strains have remained unclear. However, a preliminary analysis of the extracellular product (ECP) proteomes has revealed differences in protein compositions between low- and high-virulence strains; in addition to 1265 shared proteins, 127 proteins have been identified to be specific to one low-virulence strain and 95 proteins to be specific to two high-virulence strains. We further studied the ECP proteins of the three V. mediterranei strains from functional perspectives using integrated genomics and proteomics approaches. The results showed that lipid metabolism, transporter activity and membrane transporter pathways were more enriched in the ECPs of the two high-virulence strains than in those of the low-virulence strain. Additionally, 73 of the 95 high-virulence strain-specific proteins were found to have coding genes in the genome but were not expressed in the low-virulence strain. Moreover, comparisons with known virulence factors in the Virulence Factor Database (VFDB) and the Pathogen-Host Interactions Database (PHI-base) allowed us to predict more than 10 virulence factors in the categories of antimicrobial activity/competitive advantage, the effector delivery system and immune modulation, and the high-virulence strain-specific ECP proteins consisted of a greater percentage of known virulence factors than the low-virulence strain. Particularly, two virulence factors, MtrC and KatG, were identified in the ECPs of the two high-virulence strains but not in those of the low-virulence strain. Most coding genes of the ECP proteins including known virulence factors were identified on chromosome 1 of V. mediterranei. Our findings indicate that variations in virulence factor composition in the bacterial ECPs may partially account for the differences in the bivalve pathogenicity between V. mediterranei strains.

A giant intrinsic photovoltaic effect in atomically thin ReS2.

The photovoltaic (PV) effect in non-centrosymmetric materials consisting of a single component under homogeneous illumination can exceed the fundamental Shockley-Queisser limit compared to the traditional p-n junctions. Two-dimensional (2D) materials with a reduced dimensionality and smaller bandgap were predicated to be better candidates for the PV effect with high efficiency exceeding that of traditional ferroelectric perovskite oxides. Here, we report the giant intrinsic PV effect in atomically thin rhenium disulfide (ReS2) with centrosymmetry breaking. In graphene/ReS2/graphene sandwich structures, significant short-circuit currents (Isc) were observed with illumination over the visible spectral range, presenting the highest responsivity (110 mA W-1) and external quantum efficiency (25.7%) among those reported PV effects in 2D materials. This giant PV effect could be ascribed to the spontaneous-polarization induced depolarization field in even-number-layered ReS2 flakes benefiting from the distorted 1T lattice structure. Our results provide a new potential candidate material for the development of novel high-efficiency, miniaturized and easily integrated photodetectors and solar cells.

Oxybutynin ameliorates LPS-induced inflammatory response in human bladder epithelial cells.

Urinary tract infection (UTI) mainly results from bacterial infections in the urinary tract and markedly impacts the normal lives of millions of patients worldwide. The infection and damage to urethral epithelial cells is the first and key step of UTI development and is a critical target for treating clinical UTI. Oxybutynin, an agent for treating urinary incontinence, is recently claimed with protective effects on bladder ultrastructure. Our study will assess the impact of Oxybutynin on inflammation in lipopolysaccharide (LPS)-stimulated bladder epithelial cells. Bladder epithelial T24 cells were treated with 1 µg/mL LPS with or without 10 and 20 µM Oxybutynin for 24 h. Increased levels of oxidative stress (OS) biomarkers, such as reactive oxygen species, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, as well as upregulated inducible nitric oxide synthase and promoted release of nitric oxide, were observed in LPS-managed T24 cells, all of which were signally suppressed by Oxybutynin. Furthermore, severe inflammatory responses, including enhanced release of cytokines, upregulated matrix metallopeptidase-2 (MMP-2) and MMP-9, and raised monocyte chemoattractant protein-1 level, were found in LPS-challenged T24 cells, which were markedly reversed by Oxybutynin. Moreover, the activated toll-1ike receptor 4/nuclear factor-κB pathway observed in LPS-managed T24 cells was repressed by Oxybutynin. Collectively, Oxybutynin mitigated LPS-induced inflammatory response in human bladder epithelial cells.

Transcriptomic analysis of skin immunity genes in the Chinese spiny frog (Quasipaa spinosa) after Proteus mirabilis infection.

Recently, populations of Chinese spiny frogs (Quasipaa spinosa), an important amphibian species in China, have decreased, mainly due to a disease caused by the gram-negative bacteria Proteus mirabilis. To elucidate the immune response of the frogs, this study aimed to identify novel candidate genes functionally associated with P. mirabilis infection-induced "rotting skin" disease. Chinese spiny frogs were infected with P. mirabilis, and the skin transcriptome was sequenced using the MGISEQ-2000 platform. A total of 233,965 unigenes were obtained by sequencing, of which 27.23 % were known genes. Screening of differentially expressed genes (DEGs) indicated 210 unigenes differentially expressed after P. mirabilis infection, of which 132 unigenes were up-regulated, and 78 unigenes were down-regulated. Using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, DEGs were identified as enriched in signal pathways, such as oxidative phosphorylation, apoptosis, and the Janus kinase-signal transducer and activator of transcription pathway. Of the DEGs, there was a significant upregulation of the colony stimulating factor 2 receptor beta common subunit, interleukin 2 receptor subunit gamma, cathelicidin antimicrobial peptide, interleukin-17 receptor E, receptor-interacting serine/threonine-protein kinase 3, and pulmonary surfactant-associated protein D immune genes following P. mirabilis infection. Conversely, scavenger receptor cysteine-rich domain-containing group B protein, tumor protein p53 inducible nuclear protein 2, suppressor of cytokine signaling 2, and metalloreductase STEAP3 were significantly downregulated. In conclusion, the first skin transcriptome database of Chinese spiny frogs was established, and several immune genes were identified to elucidate the pathogenic mechanism of "skin rot" in Chinese spiny frogs and other cultured frogs.

An Inhibitor-Monitorable Single-Tube Duplex Quantitative Real-Time PCR Assay for the Detection of 'Candidatus Liberibacter asiaticus'.

Huanglongbing (HLB) is a citrus infectious disease caused by 'Candidatus Liberibacter' spp. Recently, it has begun to spread rapidly worldwide, causing significant losses to the citrus industry. Early diagnosis of HLB relies on quantitative real-time PCR assays. However, the PCR inhibitors found in the nucleic acid extracted from plant materials pose challenges for PCR assays because they may result in false-negative results. Internal standard (IS) can be introduced to establish a single-tube duplex PCR for monitoring the influence of the PCR inhibitor, but it also brings the risk of false-negative results because the amplification of IS may compete with the target. To solve this problem, we proposed a mutation-enhanced single-tube duplex PCR (mSTD-PCR) containing IS with mutant-type primers. By introducing the 3'-terminal mutation in the primer of IS to weaken its amplification reaction and its inhibition of 'Candidatus Liberibacter asiaticus' (CLas) detection, the sensitivity and quantitative accuracy of CLas detection will not be affected by IS. In evaluating the sensitivity of CLas detection using simulation samples, the mSTD-PCR showed consistent sensitivity at 25 copies per test compared with the single-plex CLas assay. The detection result of 30 leaves and 30 root samples showed that the mSTD-PCR could recognize false-negative results caused by the PCR inhibitors and reduce workload by 48% compared with the single-plex CLas assay. Generally, the proposed mSTD-PCR provides a reliable, efficient, inhibitor-monitorable, quantitative screening method for accurately controlling HLB and a universal method for establishing a PCR assay for various pathogens.

Development and Challenges of Cyclic Peptides for Immunomodulation.

Cyclic peptides are polypeptide chains formed by cyclic sequences of amide bonds between protein-derived or non-protein-derived amino acids. Compared to linear peptides, cyclic peptides offer several unique advantages, such as increased stability, stronger affinity, improved selectivity, and reduced toxicity. Cyclic peptide has been proved to have a promising application prospect in the medical field. In addition, this paper mainly describes that cyclic peptides play an important role in anti-cancer, anti-inflammatory, anti-virus, treatment of multiple sclerosis and membranous nephropathy through immunomodulation. In order to know more useful information about cyclic peptides in clinical research and drug application, this paper also summarizes cyclic peptides currently in the clinical trial stage and cyclic peptide drugs approved for marketing in the recent five years. Cyclic peptides have many advantages and great potential in treating various diseases, but there are still many challenges to be solved in the development process of cyclic peptides.

Acute Salinity Stress Disrupts Gut Microbiota Homeostasis and Reduces Network Connectivity and Cooperation in Razor Clam Sinonovacula constricta.

Accumulating evidence demonstrates that it is of great importance to maintain a stable and functional gut microbial community for host's growth and health. However, gut microenvironment is constantly affected by diverse environmental factors. Salinity can cause stress, including hypersaline or hyposaline stress to aquatic species, thereby affecting their growth conditions. Razor clam (Sinonovacula constricta), an economically important bivalve species, inhabits in intertidal and estuarine zones and constantly experiences salinity stress. Yet little is known about how and to what extent clam gut microbiota is affected by salinity stress, while this knowledge is fundamental for clam aquaculture health management. To address this concern, this study compared the temporal differences of gut bacterial signatures and community assembly of S. constricta under normal salinity (NS), low salinity (LS), and high salinity (HS) conditions. Acute salinity stress affected the compositions, structures, and functional potentials of clam gut microbial community, of which salinity stress, hours post stress, and their interaction respectively constrained 7.6%, 16.4%, and 7.9% of community variation. Phylogenetic bin-based null model result revealed that the gut bacterial assembly of three salinity groups seemed to be largely driven by stochastic processes. Network analysis indicated that gut bacterial interspecies interaction exhibited less connected and lower cooperative activity under the conditions of LS and HS compared with NS. Notably, some pathogenic bacteria, including Vibrio and Pseudoalteromonas, were identified as keystone taxa of gut microbial networks in LS and HS groups. Above findings suggest that the clams under LS and HS conditions might be at a higher risk of developing disease. Our findings enhance the mechanism understanding of gut microbial assembly in S. constricta under abiotic factor challenge, which has important implications for clam health control from a microbial ecological perspective.

Homogeneous environmental selection mainly determines the denitrifying bacterial community in intensive aquaculture water.

Nitrate reduction by napA (encodes periplasmic nitrate reductase) bacteria and nitrous oxide reduction by nosZ (encodes nitrous oxide reductase) bacteria play important roles in nitrogen cycling and removal in intensive aquaculture systems. This study investigated the diversity, dynamics, drivers, and assembly mechanisms of total bacteria as well as napA and nosZ denitrifiers in intensive shrimp aquaculture ponds over a 100-day period. Alpha diversity of the total bacterial community increased significantly over time. In contrast, the alpha diversity of napA and nosZ bacteria remained relatively stable throughout the aquaculture process. The community structure changed markedly across all groups over the culture period. Total nitrogen, phosphate, total phosphorus, and silicate were identified as significant drivers of the denitrifying bacterial communities. Network analysis revealed complex co-occurrence patterns between total, napA, and nosZ bacteria which fluctuated over time. A null model approach showed that, unlike the total community dominated by stochastic factors, napA and nosZ bacteria were primarily governed by deterministic processes. The level of determinism increased with nutrient loading, suggesting the denitrifying community can be manipulated by bioaugmentation. The dominant genus Ruegeria may be a promising candidate for introducing targeted denitrifiers into aquaculture systems to improve nitrogen removal. Overall, this study provides important ecological insights into aerobic and nitrous oxide-reducing denitrifiers in intensive aquaculture, supporting strategies to optimize microbial community structure and function.

Genome-Wide Identification of 5-HT Receptor Gene Family in Razor Clam Sinonovacula constricta and Their Circadian Rhythm Expression Analysis.

Serotonin (5-HT) is primarily distributed in the gastrointestinal and central nervous systems, where it plays a crucial role in regulating various physiological functions such as digestion, reproduction and establishing animal emotions. 5-HT is an effective oxytocin widely used in molluscan aquaculture, and its physiological functions are performed by binding to corresponding 5-HT receptors (5-HTRs). In this study, seven 5-HTR genes of Sinonovacula constricta (Sc5-HTRs) were identified and analyzed, and they were designated as Sc5-HT1A, Sc5-HT1D, Sc5-HT2-1, Sc5-HT2-2, Sc5-HT2-3, Sc5-HT4 and Sc5-HT6. Phylogenetic analysis showed that the seven Sc5-HTRs were conserved among mollusks, and the Sc5-HTRs were all transmembrane proteins. The seven Sc5-HTR genes were distributed on chromosome 1, 2, 13 and 14. After injecting 5-HT, there was a significant increase in mRNA expression levels of Sc5-HT1A (p < 0.05) and Sc5-HT2-3 (p < 0.01), while Sc5-HT4 decreased significantly (p < 0.01) compared to control groups which might be effective 5-HT receptors. Furthermore, two of the receptors (Sc5-HT2-3 and Sc5-HT4) were expressed in the circadian rhythm patterns, indicating their potential influence on the nocturnal spawning of S. constricta. Overall, these findings provide a theoretical basis for understanding the structures and functions of 5-HTR gene family members, and may facilitate the artificial propagation of mollusks.

BamA-targeted antimicrobial peptide design for enhanced efficacy and reduced toxicity.

The emergence of drug-resistant superbugs has necessitated a pressing need for innovative antibiotics. Antimicrobial peptides (AMPs) have demonstrated broad-spectrum antibacterial activity, reduced susceptibility to resistance, and immunomodulatory effects, rendering them promising for combating drug-resistant microorganisms. This study employed computational simulation methods to screen and design AMPs specifically targeting ESKAPE pathogens. Particularly, AMPs were rationally designed to target the BamA and obtain novel antimicrobial peptide sequences. The designed AMPs were assessed for their antibacterial activities, mechanisms, and stability. Molecular docking and dynamics simulations demonstrated the interaction of both designed AMPs, 11pep and D-11pep, with the ß1, ß9, ß15, and ß16 chains of BamA, resulting in misfolding of outer membrane proteins and antibacterial effects. Subsequent antibacterial investigations confirmed the broad-spectrum activity of both 11pep and D-11pep, with D-11pep demonstrating higher potency against resistant Gram-negative bacteria. D-11pep exhibited MICs of 16, 8, and 32 µg/mL against carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and multi-drug-resistant Acinetobacter baumannii, respectively, with a concomitant lower resistance induction. Mechanism of action studies confirmed that peptides could disrupt the bacterial outer membrane, aligning with the findings of molecular dynamics simulations. Additionally, D-11pep demonstrated superior stability and reduced toxicity in comparison to 11pep. The findings of this study underscore the efficacy of rational AMP design that targets BamA, along with the utilization of D-amino acid replacements as a strategy for developing AMPs against drug-resistant bacteria.

Genome-Wide Analysis of Family I84 Protease Inhibitor Genes in Three Bivalves Reveals Important Information About the Protein Family's Evolution.

Family I84 serine protease inhibitors are believed to be mollusk specific proteins involved in host defense. The molecular evolution of the family, however, remains to be understood. In this study, the genes of Family I84 protease inhibitors in 3 bivalves, Crassostrea gigas, Crassostrea virginica and Tegillarca granosa, were analyzed at the genomic level. A total of 66 Family I84 genes (22 in C. gigas, 28 in C. virginica and 16 in T. granosa) were identified from the 3 species. They distributed unevenly in the genomes involving 4 chromosomes in C. gigas and 5 chromosomes in C. virginica and T. granosa and some genes were tandemly duplicated. Most genes had 3 exons with 12 genes having 4 exons and 1 gene having 2 exons. All genes but 1 from C. gigas and 1 from T. granosa encoded peptides with a signal sequence at the N-terminus, and the properties of the predicted mature molecules were similar. Four conserved motifs were identified in the 66 amino acid sequences. Collinear analysis revealed higher collinearity between the 2 oyster species in general genes and in Family I84 genes. Phylogenetic analysis of the 66 genes with those previously reported from 3 other bivalves and 1 gastropod showed that Family I84 protease inhibitor genes from the same species tended to be grouped together in terminal branches of the constructed Maximum likelihood tree, but most internal nodes were poorly supported by the bootstrap values. In addition, differences in expression patterns between the genes of a same species were observed in the developmental stages and tissues of C. gigas and T. granosa. Moreover, the co-expression of genes within Family I84 and Family I84 genes with non-Family I84 were also detected in C. gigas and T. granosa. These results suggested that Family I84 protease inhibitor genes evolved by active duplications and structural and functional diversifications after the speciation of related mollusks, and the diversified protease inhibitor family was likely multifunctional.

Computational biology-based study of the molecular mechanism of spermidine amelioration of acute pancreatitis.

Acute pancreatitis (AP) is an acute inflammatory gastrointestinal disease, the mortality and morbility of which has been on the increase in the past years. Spermidine, a natural polyamine, has a wide range of pharmacological effects including anti-inflammation, antioxidation, anti-aging, and anti-tumorigenic. This study aimed to investigate the reliable targets and molecular mechanisms of spermidine in treating AP. By employing computational biology methods including network pharmacology, molecular docking, and molecular dynamics (MD) simulations, we explored the potential targets of spermidine in improving AP with dietary supplementation. The computational biology results revealed that spermidine had high degrees (degree: 18, betweenness: 38.91; degree: 18, betweenness: 206.41) and stable binding free energy (ΔGbind: - 12.81 ± 0.55 kcal/mol, - 15.00 ± 1.00 kcal/mol) with acetylcholinesterase (AchE) and serotonin transporter (5-HTT). Experimental validation demonstrates that spermidine treatment could reduce the necrosis and AchE activity in pancreatic acinar cells. Cellular thermal shift assay (CETSA) results revealed that spermidine could bind to and stabilize the 5-HTT protein in acinar cells. Moreover, spermidine treatment impeded the rise of the expression of 5-HTT in pancreatic tissues of caerulein induced acute pancreatitis mice. In conclusion, serotonin transporter might be a reliable target of spermidine in treating AP. This study provides new idea for the exploration of potential targets of natural compounds.