BolA-like protein (IbaG) promotes biofilm formation and pathogenicity of Vibrio parahaemolyticus.

Vibrio parahaemolyticus is a gram-negative halophilic bacterium widespread in temperate and tropical coastal waters; it is considered to be the most frequent cause of Vibrio-associated gastroenteritis in many countries. BolA-like proteins, which reportedly affect various growth and metabolic processes including flagellar synthesis in bacteria, are widely conserved from prokaryotes to eukaryotes. However, the effects exerted by BolA-like proteins on V. parahaemolyticus remain unclear, and thus require further investigation. In this study, our purpose was to investigate the role played by BolA-like protein (IbaG) in the pathogenicity of V. parahaemolyticus. We used homologous recombination to obtain the deletion strain ΔibaG and investigated the biological role of BolA family protein IbaG in V. parahaemolyticus. Our results showed that IbaG is a bacterial transcription factor that negatively modulates swimming capacity. Furthermore, overexpressing IbaG enhanced the capabilities of V. parahaemolyticus for swarming and biofilm formation. In addition, inactivation of ibaG in V. parahaemolyticus SH112 impaired its capacity for colonizing the heart, liver, spleen, and kidneys, and reduced visceral tissue damage, thereby leading to diminished virulence, compared with the wild-type strain. Finally, RNA-sequencing revealed 53 upregulated and 71 downregulated genes in the deletion strain ΔibaG. KEGG enrichment analysis showed that the two-component system, quorum sensing, bacterial secretion system, and numerous amino acid metabolism pathways had been altered due to the inactivation of ibaG. The results of this study indicated that IbaG exerts a considerable effect on gene regulation, motility, biofilm formation, and pathogenicity of V. parahaemolyticus. To the best of our knowledge, this is the first systematic study on the role played by IbaG in V. parahaemolyticus infections. Thus, our findings may lead to a better understanding of the metabolic processes involved in bacterial infections and provide a basis for the prevention and control of such infections.

White Organic Light-Emitting Diodes with External Quantum Efficiency of 20.77% at 10000 cd m-2 and Ultra-High Color Stability by Controlling Exciton Distribution.

Although brightness and efficiency have been continually improved, the inability to achieve superior efficiency, color stability, and low-efficiency roll-off simultaneously in white organic light-emitting diodes (OLEDs) remains a knotty problem restricting the commercial application. In this paper, emission balance for two different horizontal orientation emitting molecules is maintained by using hole transport materials and bipolar host materials to control carriers' recombination and exciton diffusion. Impressively, the obtained devices exhibit extremely stable white emission with small chromaticity coordinates variation of (0.0023, 0.0078) over a wide brightness range from 1000 to 50000 cd m-2. Meanwhile, the optimal white OLED realizes the power efficiency, current efficiency, and external quantum efficiency up to 70.68 lm W-1, 85.53 cd A-1, and 24.33%, respectively at the practical brightness of 1000 cd m-2. Owing to reduced heterogeneous interfaces and broadening recombination region, this device exhibits a high EQE over 20% under high luminance of 10000 cd m-2, demonstrating slight efficiency roll-off. The operating mechanism of the device is analyzed by versatile experimental and theoretical evidences, which concludes precise manipulation of charges and excitons is the key points to achieve these excellent performances. This work provides an effective strategy for the design of high-performance white OLEDs.

The constant oxidation state of Earth's mantle since the Hadean.

Determining the evolutionary history of mantle oxygen fugacity (fo2) is crucial, as it controls the fo2 of mantle-derived melts and regulates atmospheric composition through volcanic outgassing. However, the evolution of mantle fo2 remains controversial. Here, we present a comprehensive dataset of plume-derived komatiites, picrites, and ambient mantle-derived (meta)basalts, spanning from ~3.8 Ga to the present, to investigate mantle thermal and redox states evolution. Our results indicate that fo2 of both mantle plume-derived and ambient mantle-derived melts was lower during the Archean compared to the post-Archean period. This increase in the fo2 of mantle-derived melts over time correlates with decreases in mantle potential temperature and melting depth. By normalizing fo2 to a constant reference pressure (potential oxygen fugacity), we show that the fo2 of both the mantle plume and ambient upper mantle has remained constant since the Hadean. These findings suggest that secular mantle cooling reduced melting depth, increasing the fo2 of mantle-derived melts and contributing to atmospheric oxygenation.

Stability of osteotomy in minimally invasive hallux valgus surgery with "8" shaped bandage during gait: a finite element analysis.

Introduction: Hallux valgus, a common foot deformity, often necessitates surgical intervention. This study evaluates the biomechanical alterations in patients post-surgery, focusing on the efficacy of an "8" bandage fixation system to promote optimal recovery. Methods: A three-dimensional (3D) model was constructed using CT data from a patient with hallux valgus. A quasi-static finite element analysis (FEA) was conducted in conjunction with gait analysis to evaluate the biomechanical changes at the osteotomy site under "8" shaped bandage fixation following hallux valgus surgery. The effects of the "8" shaped bandage on the stability of the osteotomy site and bone healing were investigated at three load points during the gait cycle. Results: During the Loading Response (LR), Midstance (MSt), and Terminal stance TSt phases, the osteotomy end experienced maximum Von Mises stresses of 0.118, 1.349, and 1.485 MPa, respectively. Correspondingly, the maximum principal stresses, all of which were compressive along the Z-axis, were 0.11662 N, 1.39266 N, and 1.46762 N, respectively. Additionally, these phases showed a maximum relative total displacement of 0.848 mm and a maximum relative shear displacement of 0.872 mm. Conclusion: During the stance phase, the osteotomy end of the first metatarsal is predominantly subjected to compressive stress, with the relative displacement within the safe range to promote healing. The application of an "8" bandage for external fixation after surgery can maintain the dynamic stability of osteotomy sites post-minimally invasive hallux valgus correction during the gait cycle, thereby promoting the healing of the osteotomy ends.

Development of multiplex real-time PCR for simultaneous detection of SARS-CoV-2, CCoV, and FIPV.

Introduction: Coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), canine coronavirus (CCoV), and feline infectious peritonitis virus (FIPV), have the potential for interspecies transmission. These viruses can be present in complex environments where humans, dogs, and cats coexist, posing a significant threat to both human and animal safety. Methods and results: In this study, we developed a novel multiplex TaqMan-probe-based real-time PCR assay for the simultaneous detection and differentiation of SARS-CoV-2, CCoV, and FIPV. Specific primers and TaqMan fluorescent probes were designed based on the N region of SARS-CoV-2 and FIPV, as well as the S region of CCoV, which demonstrated a remarkable sensitivity and specificity toward the targeted viruses, as few as 21.83, 17.25 and 9.25 copies/µL for SARS-CoV-2, CCoV and FIPV, respectively. The standard curve constructed by the optimized method in our present study showed a high amplification efficiency within or near the optimal range of 91% to 116% and R(2) values were at least 0.95 for the abovementioned coronaviruses. A total of 91 samples, including six plasmid mixed mock samples, four virus fluid mixing simulated samples, and 81 clinical samples, were analyzed using this method. Results demonstrated strong agreement with conventional approaches. Discussion: By enabling the simultaneous detection of three viruses, this method enhances testing efficiency while decreasing costs. Importantly, it provides a valuable tool for the prevalence and geographical distribution of suspected and co-infected animals, ultimately contributing to the advancement of both animal and public health.

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome.

Metabolic syndrome (MetS) represents a constellation of metabolic abnormalities, typified by obesity, hypertension, hyperglycemia, and hyperlipidemia. It stems from intricate dysregulations in metabolic pathways governing energy and substrate metabolism. While comprehending the precise etiological mechanisms of MetS remains challenging, evidence underscores the pivotal roles of aberrations in lipid metabolism and insulin resistance (IR) in its pathogenesis. Notably, nicotinamide N-methyltransferase (NNMT) has recently surfaced as a promising therapeutic target for addressing MetS. Single nucleotide variants in the NNMT gene are significantly correlated with disturbances in energy metabolism, obesity, type 2 diabetes (T2D), hyperlipidemia, and hypertension. Elevated NNMT gene expression is notably observed in the liver and white adipose tissue (WAT) of individuals with diabetic mice, obesity, and rats afflicted with MetS. Knockdown of NNMT elicits heightened energy expenditure in adipose and hepatic tissues, mitigates lipid accumulation, and enhances insulin sensitivity. NNMT catalyzes the methylation of nicotinamide (NAM) using S-adenosyl-methionine (SAM) as the donor methyl group, resulting in the formation of S-adenosyl-l-homocysteine (SAH) and methylnicotinamide (MNAM). This enzymatic process results in the depletion of NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and the generation of SAH, a precursor of homocysteine (Hcy). Consequently, this cascade leads to reduced NAD+ levels and elevated Hcy levels, implicating NNMT in the pathogenesis of MetS. Moreover, experimental studies employing RNA interference (RNAi) strategies and small molecule inhibitors targeting NNMT have underscored its potential as a therapeutic target for preventing or treating MetS-related diseases. Nonetheless, the precise mechanistic underpinnings remain elusive, and as of yet, clinical trials focusing on NNMT have not been documented. Therefore, further investigations are warranted to elucidate the intricate roles of NNMT in MetS and to develop targeted therapeutic interventions.

Lactobacillus crispatus 7-4 Mitigates Salmonella typhimurium-Induced Enteritis via the γ­Glutamylcysteine-Mediated Nrf2 Pathway.

Salmonella typhimurium (S. typhimurium) constitutes a major public health concern. We have previously proven that Lactobacillus crispatus 7-4 (L. crispatus 7-4) can inhibit the growth of S. typhimurium and thus can be used as a biocontrol strategy to suppress foodborne S. typhimurium infections. However, the inhibitory effect and in-depth mechanism of L. crispatus 7-4 remain to be elucidated. In this study, we found that L. crispatus 7-4 can protect against S. typhimurium-induced ileum injury by promoting intestinal barrier integrity, maintaining intestinal mucosal barrier homeostasis, and reducing intestinal inflammatory response. Furthermore, we demonstrated that this probiotic strain can increase the abundance of Lactobacillus spp. to maintain microbial homeostasis and simultaneously increase the amount of γ­glutamylcysteine (γ-GC) by activating the glutathione metabolic pathway. The increased γ-GC promoted the transcription of Nrf2 target genes, thereby improving the host antioxidant level, reducing reactive oxygen species (ROS) accumulation, and removing pro-inflammatory cytokines. In other words, L. crispatus 7-4 could activate the enterocyte Nrf2 pathway by improving γ-GC to protect against S. typhimurium-induced intestinal inflammation and oxidative damage.

Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions.

The complex process of aging leads to a gradual deterioration in the function of cells, tissues, and the entire organism, thereby increasing the risk of disease and death. Nicotinamide N-methyltransferase (NNMT) has attracted attention as a potential target for combating aging and its related pathologies. Studies have shown that NNMT activity increases over time, which is closely associated with the onset and progression of age-related diseases. NNMT uses S-adenosylmethionine (SAM) as a methyl donor to facilitate the methylation of nicotinamide (NAM), converting NAM into S-adenosyl-L-homocysteine (SAH) and methylnicotinamide (MNA). This enzymatic action depletes NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and generates SAH, a precursor of homocysteine (Hcy). The reduction in the NAD+ levels and the increase in the Hcy levels are considered important factors in the aging process and age-related diseases. The efficacy of RNA interference (RNAi) therapies and small-molecule inhibitors targeting NNMT demonstrates the potential of NNMT as a therapeutic target. Despite these advances, the exact mechanisms by which NNMT influences aging and age-related diseases remain unclear, and there is a lack of clinical trials involving NNMT inhibitors and RNAi drugs. Therefore, more in-depth research is needed to elucidate the precise functions of NNMT in aging and promote the development of targeted pharmaceutical interventions. This paper aims to explore the specific role of NNMT in aging, and to evaluate its potential as a therapeutic target.

Advances in the Causes and Treatment of Floating Toes after the Weil Osteotomy: A Scoping Review.

The floating toe deformity is classified as a forefoot deformity wherein the distal portion of the toe does not establish touch with the ground, resulting in a suspended or elevated position while the finger is in a relaxed state. At first, it garnered considerable interest as a complication It is worth noting that this condition is particularly common in children under the age of 8, which usually disappears as the individual reaches maturity. Studies have shown that with the aggravation of floating toe deformity, its adverse effects on patients' gait and overall quality of life also increase. Despite the prevalence of floating toe deformity in clinical settings, there is a lack of comprehensive literature investigating its underlying causes and potential preventive strategies. This scope review follows the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) statement guidelines for scope reviews. The literature was obtained from various full-text databases, including China National Knowledge Infrastructure Database (CNKI), Wanfang Database, PubMed, and Web of Science Database. Our search focused on published literature related to floating toes, Weil osteotomy, and distal metatarsal osteotomy, up until March 1, 2023. The literature search and data analysis are conducted by two independent reviewers. If there are any disagreements, a third researcher will participate in the discussion and negotiate a decision. Furthermore, two experienced foot and ankle surgeons conducted a thorough literature analysis for this review. Sixty-two articles were included. Through the clinical analysis of the structural changes of the forefoot before and after operation, the classification of floating toe was described, the causes of pathological floating toe were summarized, and the possible intervention measures for the disease were put forward under the advice of foot and ankle surgery experts. We comprehensively summarize the current knowledge system about the etiology of floating toe and put forward the corresponding intervention strategy. We recommend that future studies will focus on the improvement of surgical procedures, such as the combination of Weil osteotomy, proximal interphalangeal (PIP) arthrodesis and flexor tendon arthrodesis.

Secondary hemophagocytic syndrome in an acquired immunodeficiency syndrome and Alpha-thalassemia patient infected with Talaromyces marneffei: A case report and literature review.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by a hyperinflammatory syndrome and impairment of multiple organ systems. Talaromycosis marneffei (TSM) is an opportunistic infection mostly found in immunosuppressed populations, such as those with acquired immunodeficiency syndrome (AIDS), and is prevalent in southern China. However, HLH secondary to TSM is extremely rare and has only been reported in isolated cases. A 30-year-old patient with recurrent high fever and progressive cytopenia was diagnosed with HLH secondary to disseminated TSM with AIDS and Alpha-thalassemia. The patient remained in sustained remission without recurrence after effective treatment with antifungals and glucocorticoids.