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There is a lack of research on how Tibetan kefir grains fermentation alters the physicochemical properties and biological activity of Lycium barbarum pulp polysaccharides, despite some reports that fermentation can affect the structure and activity of plant polysaccharides. This study demonstrated that, through fermentation, the molecular weight of polysaccharides decreased from 25.33 to 15.11 kg/mol while the contents of total sugar and uronic acid increased by 19.11% and 40.38%, respectively. Furthermore, after fermentation, the polysaccharides exhibited an uneven and rough surface along with a reduced number of branched chains and triple helix structures. Tibetan kefir grains fermentation enhanced the antioxidant activity of polysaccharides, which may be attributed to an increase in arabinose, galactose, and uronic acid content and a decrease in polysaccharide molecular weight. This research offers an alternative viewpoint on the potential application of Tibetan kefir grains-fermented Lycium barbarum pulp polysaccharides in functional foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This prospective cohort study, conducted at the Fenglin Community Health Service Center (FCHC) in Xuhui District, Shanghai, aimed to investigate the impact of maternal psychological status on offspring neurodevelopment., Methods: A total of 430 mother-child pairs were included, with pregnant women enrolled between February 18, 2020, and April 19, 2021. Face-to-face interviews and electronic data collection on demographic characteristics, health conditions and medical history were employed at various stages of pregnancy and postpartum. Maternal depression and anxiety were assessed using the PHQ-9 and GAD-7 scales, while offspring neurodevelopment was measured at six months using the Ages and Stages Questionnaire 3rd Edition (ASQ-3). In statistical analyses, group-based trajectory modeling (GBTM) was employed to identify the latent groups for maternal psychological trajectories, including depression and anxiety, and logistic regression was used to explore associations between maternal psychological trajectories and offspring neurodevelopment, adjusting for potential confounders., Results: Five latent trajectory groups were identified for both depression and anxiety, exhibiting distinct patterns over time. Results indicated that maternal psychological trajectories were associated with various domains of offspring neurodevelopment, including communication, problem-solving, personal-social, and gross motor skills. Specifically, mothers in trajectory groups characterized by the highest level of depression or anxiety showed increased odds of offspring neurodevelopmental delays compared to reference groups., Conclusion: Our findings underscore the importance of maternal mental health during the perinatal period and highlight the potential implications for offspring neurodevelopment. Further research is warranted to elucidate underlying mechanisms and inform targeted interventions to support maternal mental well-being and optimize offspring outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multidrug resistance (MDR) Klebsiella pneumoniae (K. pneumoniae) is a major emerging threat to human health, and leads to very high mortality rate. The effectiveness of colistin, the last resort against MDR Gram-negative bacteria, is significantly compromised due to the widespread presence of plasmid- or chromosome-mediated resistance genes. In this study, o-cymen-5-ol has been found to greatly restore colistin sensitivity in MDR K. pneumoniae. Importantly, this compound does not impact bacterial viability, induce resistance, or cause any noticeable cell toxicity. Various routes disclosed the potential mechanism of o-cymen-5-ol potentiating colistin activity against MDR K. pneumoniae. These include inhibiting the activity of plasmid-mediated mobile colistin resistance gene (mcr-1), accelerating lipopolysaccharide (LPS) - mediated membrane damage, and promoting the ATP-binding cassette (ABC) transporter pathway. To enhance the administration and bioavailability of o-cymen-5-ol, a nanoemulsion has been designed, which significantly improves the loading efficiency and solubility of o-cymen-5-ol, resulting in antimicrobial potentiation of colistin against K. pneumoniae infection. This study has revealed a new understanding of the o-cymen-5-ol nanoemulsion as a means to enhance the effectiveness of colistin against resistant factors. The finding also suggests that o-cymen-5-ol nanoemulsion could be a promising approach in the development of potential treatments for multidrug-resistant Gram-negative bacterial infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Given expanding studies in epidemiology and disease-oriented human studies offering hundreds of associations between the human "ome" and disease, prioritizing molecules relevant to disease mechanisms among this growing breadth is important. Here, we link the circulating proteome to human heart failure (HF) propensity (via echocardiographic phenotyping and clinical outcomes) across the lifespan, demonstrating key pathways of fibrosis, inflammation, metabolism, and hypertrophy. We observe a broad array of genes encoding proteins linked to HF phenotypes and outcomes in clinical populations dynamically expressed at a transcriptional level in human myocardium during HF and cardiac recovery (several in a cell-specific fashion). Many identified targets do not have wide precedent in large-scale genomic discovery or human studies, highlighting the complementary roles for proteomic and tissue transcriptomic discovery to focus epidemiological targets to those relevant in human myocardium for further interrogation., Competing Interests: Declaration of interests S.G.D. is a consultant for Abbott, and S.G.D. and K.J.L. have industry research support from Novartis. R.V.S. has served as a consultant for Amgen, Cytokinetics, and Thryv Therapeutics (with options ownership in Thryv). R.V.S. is a co-inventor on a patent for ex-RNA signatures of cardiac remodeling and a pending patent on proteomic signatures of fitness and lung and liver diseases. R.V.S. also has stock options with Thryv Therapeutics. A.S.P. is a co-inventor on a pending patent for proteomic signatures of fitness, lung, and liver diseases. K.A. does ad hoc consulting for Tegus and Guidepoint and serves on a DSMB for Fortrea. M.N. has received speaking honoraria from Cytokinetics. K.J.L. serves as a consultant for Medtronic, Implicit Biosciences, Kiniksa Pharmaceuticals, and Cytokinetics. K.J.L. receives grant support from Amgen, Novartis, Kiniksa Pharmaceuticals, and Implicit Biosciences. S.D. is a co-founder and has equity in Thryv therapeutics and Switch Therapeutics. S.D. has received grant support from Abbot Laboratories and Bristol Myers Squib. S.D. is a co-inventor on a patent on tissue-specific EV-RNAs. R.K. has received personal fees from GSK, Astrazeneca, Boehringer Ingelheim, and CVS Caremark. S.J.S. has received consulting fees from 35Pharma, Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, BaroPace, Bayer, Boehringer-Ingelheim, Boston Scientific, BridgeBio, Bristol Myers Squibb, Corvia, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, eMyosound, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, ReCor, Regeneron, Rivus, SalubriusBio, Sardocor, Shifamed, Tectonic, Tenax, Tenaya, Ulink, and Ultromics. J.M.A. was employed by Amgen. J.W. reports consulting/scientific advisory board for Abiomed, Abbott, Astra Zeneca, Boehringer Ingelheim, and Cytokinetics within the last 24 months., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Foxtail millet and sourdough are used to make foxtail millet sourdough steamed bread to improve the flavor and taste. Compared with the conventional freeze-thaw treatment (CFT), the effect of magnetic field-assisted freeze-thaw treatment (MFT) on the storage quality of foxtail millet sourdough and steamed bread is explored. The results showed that compared with CFT, MFT shortened the phase transition time of dough; decreased the water loss rate, the water mobility, and the freezable water content; increased the fermentation volume; stabilized the rheological properties; and minimized the damage of freezing and thawing to the secondary structure and microstructure of the gluten. In addition, an analysis of the specific volume, texture, surface color, and texture structure showed that MFT was beneficial to slowing the deterioration of the steamed bread texture. Finally, MFT effectively inhibited the growth and recrystallization of ice crystals during freezing and thawing, improving the quality of millet dough and steamed bread., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: TANK-binding kinase 1 (TBK1) is a pivotal mediator of innate immunity, activated by receptors such as mitochondrial antiviral signaling protein (MAVS), stimulator of interferon genes (STING), and TIR-domain-containing adaptor inducing interferon-β (TRIF). It modulates immune responses by exerting influence on the type I interferons (IFN-Is) signaling and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, Over the past few years, TBK1 multifaceted role in both immune and inflammatory responses is increasingly recognized., Methods and Results: This review aims to scrutinize how TBK1 operates within the NF-κB pathway and the interferon regulatory transcription factor 3 (IRF3)-dependent IFN-I pathways, highlighting the kinases and other molecules involved in these processes. This analysis reveals the distinctive characteristics of TBK1's involvement in these pathways. Furthermore, it has been observed that the role of TBK1 in exerting anti-inflammatory or pro-inflammatory effects is contingent upon varying pathological conditions, indicating a multifaceted role in immune regulation., Discussion: TBK1's evolving role in various diseases and the potential of TBK1 inhibitors as therapeutic agents are explored. Targeting TBK1 may provide new strategies for treating inflammatory disorders and autoimmune diseases associated with IFN-Is, warranting further investigation.

In this study, the effects of the Cd-resistant and pyoverdine-producing strain Pseudomonas umsongensis CR14 on Cd stabilization and the mechanisms were investigated. Compared with the control, CR14 markedly reduced the Cd concentration in a Cd-containing solution. The genes pvdA, 4498, 4499, and pchF, which are associated with pyoverdine production, were identified in CR14. Subsequently, CR14 and the CR14ΔpvdA, CR14Δ4498, CR14Δ4499, and CR14ΔpchF mutants were characterized for their effects on Cd stabilization in solution. After 72 h of incubation, the CR14ΔpchF and CR14ΔpvdA mutants significantly decreased Cd concentrations compared with CR14. Notably, the CR14ΔpvdA mutant showed a greater impact on Cd stabilization than the other mutants. Compared with CR14, this mutant brought a lower Cd concentration in the solution, with higher levels of cell surface-adsorbed and intracellular accumulated Cd, content of lipopolysaccharide (LPS), expression of the LPS-producing genes lptD and lpxL, and cell surface particles. Additionally, compared with CR14, the CR14ΔpvdA mutant demonstrated increased interactions between the hydroxyl, carboxyl, amino, or ether groups and Cd. These results suggest that the CR14ΔpvdA mutant immobilized Cd by increasing LPS production and cell surface particle numbers, upregulating the expression of LPS-producing genes, and increasing cell surface adsorption and intracellular accumulation in Cd-polluted solutions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Non-genetic mechanisms have recently emerged as important drivers of anticancer drug resistance. Among these, the drug tolerant persister (DTP) cell phenotype is attracting more and more attention and giving a predominant non-genetic role in cancer therapy resistance. The DTP phenotype is characterized by a quiescent or slow-cell-cycle reversible state of the cancer cell subpopulation and inert specialization to stimuli, which tolerates anticancer drug exposure to some extent through the interaction of multiple underlying mechanisms and recovering growth and proliferation after drug withdrawal, ultimately leading to treatment resistance and cancer recurrence. Therefore, targeting DTP cells is anticipated to provide new treatment opportunities for cancer patients, although our current knowledge of these DTP cells in treatment resistance remains limited. In this review, we provide a comprehensive overview of the formation characteristics and underlying drug tolerant mechanisms of DTP cells, investigate the potential drugs for DTP (including preclinical drugs, novel use for old drugs, and natural products) based on different medicine models, and discuss the necessity and feasibility of anti-DTP therapy, related application forms, and future issues that will need to be addressed to advance this emerging field towards clinical applications. Nonetheless, understanding the novel functions of DTP cells may enable us to develop new more effective anticancer therapy and improve clinical outcomes for cancer patients., (© 2024. The Author(s).)

Phytoremediation coupled with agroproduction (PCA) model contributes to sustainable agriculture and environmental management. This study investigated the impact of continuous cropping early/late season rice (RR) and Sedum alfredii-rice rotation (SR) on soil physical and chemical properties, as well as their relationships with soil microbial community. In 2022, SR treatment significantly increased pH value and organic matter content by 7 % and 17 %, respectively, compared to the levels in 2020, while RR treatment showed no change. RR treatment resulted in a significant decrease in soil concentrations of Ca, Mg, and K by 18.42 %, 29.01 %, and 7.77 %, respectively. Furthermore, SR treatment saw reductions of 29.62 % in total Cd and 38.30 % in DTPA extractable Cd in the soil. Over the two years, both treatments notably influenced the diversity, structure, and network of the rhizosphere bacterial and fungal communities, which are crucial for nutrient cycling and plant health. Notably, SR treatment exhibited a more complex network compared to RR, suggesting a greater impact on the interconnected systems. Therefore, these findings highlight the potential of Sedum rotation system to rehabilitate contaminated soils while supporting agricultural practices, which is essential for food security and environmental sustainability. This research direction holds promise for future exploration and application in the fields of phytoremediation and agroecology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In this study, the Pb-resistant Ensifer adhaerens strain S24, which contains quorum sensing (QS) systems responsible for N-acyl homoserine lactone (AHL) production, was investigated for QS system-mediated Pb stabilization and the underlying mechanisms. Whole-genome sequence analysis revealed the QS SinI/R and TraI/R systems in strain S24. Subsequently, strains S24 and the S24∆sinI/R, S24∆traI/R, S24∆traI/R/sinR, and S24∆sinI/R-traI/R/sinR mutants were constructed and compared for QS SinI/SinR-TraI/TraR system-mediated Pb stabilization in the solution and the mechanisms involved. After 5 days of incubation, strain S24 significantly decreased the Pb concentration in the Pb-contaminated solution compared with the mutants. The S24∆sinI/R-traI/R/sinR mutant exhibited reduced Pb stabilization and AHL activity than the other mutants. The S24∆sinI/R-traI/R/sinR mutant had significantly greater Pb concentrations in the solution and lower cell surface-adsorbed and extracellular precipitated Pb (PbS) contents as well as lower expression of H 2 S-producing genes of metC and sseA than did strain S24. Furthermore, the S24∆sinI/R-traI/R/sinR mutant displayed reduced interactions between the hydroxyl, amino, carboxyl, and ether groups and Pb, compared with strain S24. These findings implied the vital role of the SinI/SinR-TraI/TraR systems in strain S24 for Pb stabilization through enhanced cell surface adsorption and extracellular precipitation in Pb-polluted aquatic environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Medicago sativa polysaccharides (MSPs) are beneficial compounds extracted from Medicago sativa L. that exhibit multiple medicinal activities. However, little is known about their hypoglycemic effects. In this study, MSP-II-a, a neutral polysaccharide with an Mw of 4.3 × 104 Da, was isolated and purified from M. sativa L. Monosaccharide composition analysis determined that MSP-II-a was composed of arabinose, glucose, galactose, mannose, rhamnose, and xylose in a molar ratio of 2.1:4.0:1.1:0.4:1.4:1.1. Structural characterization of MSP-II was performed using a combination of methylation analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results showed that MSP-II-a was mainly comprised of 1,4-p-Glc, 1,3,4-Rha, and 1,3-p-Gal glycosidic linkages, revealing a mesh-like texture with irregular blade shapes. In vitro assays demonstrated that MSP-II-a, at concentrations of 200 and 400 μg/mL, promoted glucose uptake in insulin-resistant 3T3-L1 adipocytes. In vivo studies have shown that MSP-II-a significantly alleviates insulin resistance by reducing fasting blood glucose levels and increasing hepatic glycogen synthesis in HFD/STZ-induced diabetic mice. These findings revealed that MSP-II-a is a promising source of bioactive polysaccharides with potential hypoglycemic activity., (© 2024 Wiley‐VCH GmbH.)

Fullerene (C 60 ) crystals have attracted considerable attention in the field of optoelectronic devices owing to their excellent performance as n-type semiconductor material. However, a challenge still remains unbeaten as to the continuous crystallization of non-solvated C 60 single-crystal films with high coverage and uniform alignment using low-cost solution techniques. Here, a facile bar coating method is used to prepare ribbon-shaped non-solvated C 60 crystals with a large area (up to centimeters) and high coverage (>95%) by precisely controlling the crystallization process from specific solvents. Benefiting from the non-solvated crystalline structure, well-distributed thickness, uniform morphological alignment, and crystallographic orientation, organic field-effect transistors fabricated from the C 60 single-crystal films exhibit a high average electron mobility of 2.28 cm 2  V -1 s -1 , along with the coefficient of variance (CV) as small as 13.6%. This efficient manufacturing method will lay a strong foundation for C 60 single-crystal films to fit into the future high-performance integrated optoelectronic application., (© 2024 Wiley‐VCH GmbH.)

Objective: The objective of this study was to identify the transcriptional landscape of insulin resistance (IR) in subcutaneous adipose tissue (SAT) in humans across the spectrum of obesity., Methods: We used SAT RNA sequencing in 220 individuals with metabolic phenotyping., Results: We identified a 35-gene signature with high predictive accuracy for homeostatic model of IR that was expressed across a variety of non-immune cell populations. We observed primarily "protective" IR associations for adipocyte transcripts and "deleterious" associations for macrophage transcripts, as well as a high concordance between SAT and visceral adipose tissue (VAT). Multiple SAT genes exhibited dynamic expression 5 years after weight loss surgery and with insulin stimulation. Using available expression quantitative trait loci in SAT and/or VAT, we demonstrated similar genetic effect sizes of SAT and VAT on type 2 diabetes and BMI., Conclusions: SAT is conventionally viewed as a metabolic buffer for lipid deposition during positive energy balance, whereas VAT is viewed as a dominant contributor to and prime mediator of IR and cardiometabolic disease risk. Our results implicate a dynamic transcriptional architecture of IR that resides in both immune and non-immune populations in SAT and is shared with VAT, nuancing the current VAT-centric concept of IR in humans., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Self-assembled Eu-dipeptide (tryptophan-phenylalanine) microparticles with multi-emission fluorescence was prepared and modified with a single-stranded DNA corresponding to the sulfamethazine (SMZ) adapter (Eu-PMPs@cDNA). Aptamer-functionalized magnetic Fe 3 O 4 (MNPs@aptamer) was used to specifically bind the target SMZ. Using Eu-PMPs@cDNA as fluorescent signal probe and MNPs@aptamer as catcher, a noncompetitive fluorescence sensing strategy was developed for determination of SMZ with good sensitivity, accuracy, selectivity, and stability. Under the optimized conditions, fluorescence increases linearly in the 0-20 ng/mL SMZ concentration range, and the detection limit is 0.014 ng/mL. The fluorescence sensing method was applied to analysis of water and fish muscle samples, and recoveries ranged from 81.78 to 119.46 % with relative standard deviations below 4.2 %. This study offered a reliable and sensitive fluorescence sensing strategy for SMZ determination in food samples, which owns great potential for wide-ranging application in harmful compounds assay by simply changing the type of aptamer and its complementary single-stranded DNA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Findings regarding the relationship between sarcopenia and lymphoma have been inconsistent across studies. This study investigated the association between sarcopenia and lymphoma. We systematically searched the Embase, Science Direct, Cochrane Library, and PubMed databases from inception to 31 March 2024 to identify relevant studies. Two researchers independently extracted and evaluated studies that met inclusion and exclusion criteria. Twenty-six studies with 3659 participants were included. Sarcopenic lymphoma patients had poor overall survival (OS) (HR = 1.88; 95% CI: 1.47-2.41; p  < 0.001). The heterogeneity was high (I 2 =80%). However, the result of the Egger test indicated a significant publication bias ( p  < 0.001). After employing the trim and fill method to adjust for this bias, the HR of OS became non-significant ( p  > 0.05). The progression-free survival (PFS) was worse in sarcopenic patients (HR = 1.77; 95% CI: 1.37-2.29; p  < 0.001; I 2 =70%). There was no significant publication bias ( p  > 0.05). In the subgroup analyses, sarcopenia was a negative predictor of OS in lymphoma patients who undergo hematopoietic cell transplantation (HCT) (HR  = 1.61;95% CI: 1.19-2.18; I 2 =30%). Male lymphoma patients with sarcopenia had a significantly worse OS (HR = 2.29; 95% CI:1.24-4.24; p  = 0.009). Among patients with primary central nervous system lymphoma (PCNSL), those with sarcopenia defined by temporal muscle thickness (TMT) exhibited significantly worse OS (HR = 2.20; 95% CI:1.04-4.65; p  = 0.039; I 2 =68%). Sarcopenia is associated with worse PFS in lymphoma patients. Subgroup analyses indicate that sarcopenia is a negative predictor of OS after HCT, and male lymphoma patients who suffer from sarcopenia have higher mortality. Sarcopenia defined by TMT is also a negative predictor of OS for patients with PCNSL.

Background: Polymyxin E is widely recognized as a last resort for treating multidrug-resistant gram-negative bacteria. Unfortunately, the effectiveness of polymyxin E is significantly reduced when treating life-threatening bacterial infections due to plasmid-mediated polymyxin E resistance. The synergistic effect of applying a polymyxin E adjuvant is a promising strategy for overcoming the growing threat of antibiotic-resistant pathogens., Purpose: To evaluate the synergistic effect of fisetin and polymyxin E on S. typhimurium infections in vivo and further elucidate the underlying mechanism of this effect., Methods: The effect of combining fisetin and polymyxin E to treat mobilized colistin resistance-1-positive (MCR-1-positive) gram-negative bacteria in vitro was examined using various methods, such as checkerboard assays, growth curves and time‒kill curves. To elucidate the mechanism by which fisetin affects MCR-1, we employed ultraviolet (UV) absorption spectroscopy, thin layer chromatography (TLC), and western blot analysis to investigate its effect at the protein level. Subsequently, molecular dynamics simulations (MDS) and metabolomics analysis were utilized to determine the site of interaction between fisetin and MCR-1 as well as the potential pathways and mechanisms involved. A new nanoemulsion of fisetin was produced using high-pressure homogenization, and its stability was tested. Finally, two animal models of S. typhimurium HYM2 infection were established to evaluate the synergistic effect of polymyxin E and fisetin in vivo., Results: Our study revealed that fisetin exhibited a synergistic effect when combined with polymyxin E against MCR-1-positive S. typhimurium. The TLC results demonstrated that fisetin could inhibit the phosphoethanolamine (PEA) transfer of the MCR-1 protein, thereby restoring the activity of polymyxin E in strains against MCR-1. The MDS analysis indicated robust and immediate binding between fisetin and the MCR-1 protein, with both hydrophobic and polar effects playing significant roles in determining the binding energy of the former. Metabolomic studies demonstrated that the addition of fisetin significantly modulated bacterial metabolites. Moreover, it effectively inhibited the activity of ABC transporters in bacteria, thereby mitigating bacterial drug resistance and enhancing the therapeutic efficacy of polymyxin E. Furthermore, in mouse and chick models of infection, intragastric administration of the fisetin nanoemulsion together with polymyxin E resulted in significant therapeutic benefits, including increased survival rates, reduced bacterial colonization, and decreased levels of inflammatory factors., Conclusion: Fisetin, an MCR-1 inhibitor and a promising synergistic partner of polymyxin E, has significant potential for clinical application in the treatment of S. typhimurium infections, particularly those resulting extensively from drug-resistant MCR-1-positive strains., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: Tracheal adenoid cystic carcinoma (ACC) is a slow growing yet aggressive malignancy with high rates of local recurrence as well as distant metastasis. Tracheal ACC exhibit a low mutation burden along with high mutational diversity, and generally do not respond well to chemotherapeutics., Methods: We present a rare case of primary tracheal ACC initially presenting with nonspecific cervicalgia and globus sensation that was ultimately treated with tracheal resection followed by chemoradiation. Immune profiling of intratumoral T-cell receptor (TCR) repertoire was subsequently performed using single cell RNA sequencing (scRNAseq)., Results: We describe a rare case of primary tracheal adenoid cystic carcinoma highlighting several management principles as well as providing new insights into intratumor T cell populations., Conclusions: Primary tracheal ACC is most commonly treated with surgical resection followed by adjuvant therapy. Further characterization of the tumor immune microenvironment is necessary to better understand ACC disease biology and to identify potential therapeutic targets., (© 2024 Wiley Periodicals LLC.)

Background: The morphology of proximal humeral fractures (PHFs) is complex, and the fixation and selection of implants need to be guided by the fracture type and classification, which requires an accurate understanding of the fracture line. This study had three purposes. 1) Define and analyze the fracture lines and morphological features of all types PHFs by three-dimensional (3D) mapping technology. 2) Determine the osteotomy position of the biomechanical model of the PHFs according to the fracture heat map. 3) Based on the analysis of the pathological morphology and distribution of a large number of consecutive cases of PHFs, propose a novel classification of PHFs. Methods: We retrospectively collected 220 cases of PHFs and generated a 3D fracture map and heat map based on computed tomography (CT) imaging. Through analysis of the fracture morphology of the 220 PHFs, a novel classification was proposed. The primary criterion for staging was the continuity between the humeral head and the greater tuberosity and lesser tuberosity, and the secondary criterion was the relationship between the humeral head segment and the humeral shaft. Results: The fracture line was primarily found around the metaphyseal zone of region of the surgical neck, with the most extensive distribution being below the larger tuberosity and on the posterior medial side of the epiphysis. We suggest that the osteotomy gap should be immediately (approximately 5-10 mm) below the lower edge of the articular surface. The most common type of fracture was type I3 (33 cases, 15.0%), followed by type IV3 fracture (23 cases, 10.4%), and type III2 fracture (22 cases, 10.0%). Interobserver and intraobserver reliability analysis for the fracture classification revealed a k value (95% confidence interval) of 0.639 (0.57-0.71) and 0.841, P < 0.01, respectively. Conclusion: In this study, the fracture line and morphological characteristics of PHFs were clarified in detail by 3D mapping technique. In addition, a new classification method was proposed by analysis of the morphological characteristics of 220 PHFs, A two-part fracture model for PHFs is also proposed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhang, Ding, Zhang, Sheng and Piao.)

Background: Cardiac allograft vasculopathy (CAV), a diffuse thickening of the intima of the coronary arteries and microvasculature, is the leading cause of late graft failure and mortality after heart transplantation (HT). Diagnosis involves invasive coronary angiography, which carries substantial risk, and minimally-invasive approaches to CAV diagnosis are urgently needed. Using single-cell RNA-sequencing in peripheral blood mononuclear cells (PBMCs), we sought to identify cell-specific gene expression profiles in CAV., Methods: Whole blood was collected from 22 HT recipients with angiographically-confirmed CAV and 18 HT recipients without CAV. PBMCs were isolated and subjected to single-cell RNA-sequencing using a 10X Genomics microfluidic platform. Downstream analyses focused on differential expression of genes, cell compositional changes, and T cell receptor repertoire analyses., Results: Across 40 PBMC samples, we isolated 134,984 cells spanning 8 major clusters and 31 subclusters of cell types. Compositional analyses showed subtle, but significant increases in CD4+ T central memory cells, and CD14+ and CD16+ monocytes in high-grade CAV (CAV-2 and CAV-3) as compared to low-grade or absent CAV. After adjusting for age, gender, and prednisone use, 745 genes were differentially expressed in a cell-specific manner in high-grade CAV. Weighted gene co-expression network analyses showed enrichment for putative pathways involved in inflammation and angiogenesis. There were no significant differences in T cell clonality or diversity with increasing CAV severity., Conclusions: Unbiased whole transcriptomic analyses at single-cell resolution identify unique, cell-specific gene expression patterns in CAV, suggesting the potential utility of peripheral gene expression biomarkers in diagnosing CAV.

Soft pneumatic actuation is widely used in wearable devices, soft robots, artificial muscles, and surgery machines. However, generating high-pressure gases in a soft, controllable, and portable way remains a substantial challenge. Here, a class of programmable chemical reactions that can be used to controllably generate gases with a maximum pressure output of nearly 6 MPa is reported. It is proposed to realize the programmability of the chemical reaction process using thermoelectric material with programmable electric current and employing preprogrammed reversible chemical reactants. The programmable chemical reactions as soft pneumatic actuation can be operated independently as miniature gas sources (∼20-100 g) or combined with arbitrary physical structures to make self-contained machines, capable of generating unprecedented pressures of nearly 6 MPa or forces of about 18 kN in a controllable, portable, and silent manner. Striking demonstrations of breaking a brick, a marble, and concrete blocks, raising a sightseeing car, and successful applications in artificial muscles and soft assistive wearables illustrate tremendous application prospects of soft pneumatic actuation via programmable chemical reactions. The study establishes a new paradigm toward ultrastrong soft pneumatic actuation., (© 2024 Wiley‐VCH GmbH.)

Background: Retroperitoneal lymphatic malformations (LMs) are rare. Currently, the treatment of retroperitoneal LMs remains challenging. This study aimed to examine the safety and efficacy of laparoscopic-assisted sclerotherapy for retroperitoneal LMs in pediatric patients., Methods: We retrospectively reviewed patients treated with laparoscopic-assisted sclerotherapy for retroperitoneal LMs in a single tertiary medical center between July 2020 and February 2023. Doxycycline was prepared into a solution with a concentration of 10 mg/ml for use in sclerotherapy. Demographic data, clinical features, details of management, and outcomes were collected and analyzed., Results: A total of six patients, comprising three males and three females, were identified. The LMs were categorized into four macrocystic and two mixed-cystic types. The mean age and weight were 52.2 months (range, 11-108 months) and 20 kg (range, 12.5-27.5 kg), respectively. Three patients presented with abdominal pain or distension, while the other three patients were asymptomatic. All six patients underwent a total of eight sclerotherapy sessions. Two patients experienced intra-cystic hemorrhage and required a second sclerotherapy session. Only one patient presented with vomiting after sclerotherapy, which resolved spontaneously. Five patients met the complete response criteria, and one patient met the effective criteria. The mean reduction in lesion size was 92.3% (range, 69.9%-99.6%). No further complications or recurrence were recorded during follow-up., Conclusion: Laparoscopic-assisted sclerotherapy is a safe and effective approach for treating retroperitoneal LMs. This technique is applicable for both macrocystic and mixed-cystic retroperitoneal LMs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Shi, Lv, Xu, Liu, Sheng, Ren and Chen.)

Proximal humerus fractures (PHFs) are common in the elderly and usually involve defects in the medial column.The current standard for medial column reconstruction is a lateral locking plate (LLP) in combination with either an intramedullary fibula support or an autogenous fibula graft. However, autogenous fibula graft can lead to additional trauma for patients and allogeneic fibular graft can increase patients' economic burden and pose risks of infection and disease transmission. The primary objective of this study was to introduce and assess a novel "Sandwich" fixation technique and compare its biomechanical properties to the traditional fixation methods for PHFs. In this study, we established finite element models of two different internal fixation methods: LLP-intramedullary reconstruction plate with bone cement (LLP-IRPBC) and LLP-intramedullary fibula segment (LLP-IFS). The biomechanical properties of the two fixation methods were evaluated by applying axial, adduction, abduction, torsional loads and screw extraction tests to the models. These FEA results were subsequently validated through a series of biomechanical experiments. Under various loading conditions such as axial, adduction, abduction, and rotation, the LLP-IRPBC group consistently demonstrated higher structural stiffness and less displacement compared to the LLP-IFS group, regardless of whether the bone was in a normal (Nor) or osteoporotic (Ost) state. Under axial, abduction and torsional loads, the maximum stress on LLPs of LLP-IRPBC group was lower than that of LLP-IFS group, while under adduction load, the maximum stress on LLPs of LLP-IRPBC group was higher than that of LLP-IFS group under Ost condition, and almost the same under Nor condition. The screw-pulling force in the LLP-IRPBC group was 1.85 times greater than that of the LLP-IFS group in Nor conditions and 1.36 times greater in Ost conditions. Importantly, the results of the biomechanical experiments closely mirrored those obtained through FEA, confirming the accuracy and reliability of FEA. The novel "Sandwich" fixation technique appears to offer stable medial support and rotational stability while significantly enhancing the strength of the fixation screws. This innovative approach represents a promising strategy for clinical treatment of PHFs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lv, Zhang, Qv, Sheng, Zhang and Piao.)

Tea plant ( Camellia sinensis [ L .]) is one of the most important crops in China, and tea branch is an important agronomic trait that determines the yield of tea plant. In previous work focused on GWAS that detecting GWAS signals related to plant architecture through whole genome re-sequencing of ancient tea plants, a gene locus TEA 029928 significantly related to plant type was found. Sequence alignment results showed that this gene belonged to the F-box family. We named it CsBRC . CsBRC-GFP fusion proteins were mainly localized in the plasma membrane. By comparing the phenotypes of CsBRC transgenic tobacco and WT tobacco, it was found that the number of branches of transgenic tobacco was significantly higher than that of wild-type tobacco. Through RNA-seq analysis, it was found that CsBRC affects the branching development of plants by regulating the expression of genes related to brassinosteroid synthesis pathway in plants. In addition, overexpression of CsBRC in rice could increase tiller number, grain length and width, and 1,000-grain weight., Competing Interests: The authors declare that they have no competing interest., (© 2024 The Author(s). Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Purpose: To present the process from acute Posner-Schlossman syndrome (PSS) relapse to remission under 2% ganciclovir (GCV), corticosteroids and anti-glaucoma agents on 323 patients., Methods: A retrospective study enrolling 323 PSS patients. Demographics and ophthalmic examination results were generated. Patients were treated with GCV, corticosteroids and anti-glaucoma agents andfollowed up every 2-6 weeks., Results: Patients were divided into the GCV monotherapy ( N  = 65, 20.12%), GCV and corticosteroids (G+C, N  = 106) and GCV, corticosteroid and IOP-lowering drugs (G+C+L, N  = 152) group. The G+C+L group had the highest intraocular pressure (IOP, 26.33 ± 10.26 mmHg, P  < 0.001) and largest cup-to-disc ratio (0.58 ± 0.19, P  < 0.05). After treatment, IOP of three groups dropped to similar level. Ninety-nine (30.65%) patients were corticosteroid-dependent whose daily corticosteroid consumption decreased after using GCV (from 2.23 ± 1.02 to 0.97 ± 0.98 drops/day)., Conclusion: 2% GCV solutions worked effectively on PSS relapse with corticosteroids and anti-glaucoma agents. In patients suspected of CMV infection, proper GCV could reduce the chance of corticosteroid dependence.

Purpose: This study focused on the prevalence, unique features, and required treatment of steroid-dependent Posner-Schlossman syndrome (SD-PSS), and analyzed the outcome of 2% Ganciclovir and gradual decrement steroid combination therapy in SD-PSS patients., Methods: Retrospective comparative and interventional study. SD-PSS was defined as PSS patients with continuous steroid use for over 3 months and relapsed within 2 weeks after steroid withdrawal or tapered dosage. Totally 74 SD-PSS eyes were compared with 78 randomly chosen non-steroid dependent PSS eyes. SD-PSS patients who underwent 2% GCV and gradual decrement steroid therapy with at least two follow-ups ( n  = 50) were analyzed for the treatment outcome., Results: The prevalence of SD-PSS is 26.87% (97/361) in our PSS patients. SD-PSS patients demonstrated significantly younger onset age, longer disease course, higher intraocular pressure (IOP), and higher degree of iris depigmentation at the first visit. They required significantly more IOP-lowering medication and stronger steroid after the first visit. Our 2% GCV and gradual decrement steroid therapy helped 66% (33/50) SD-PSS patients with steroid withdrawal (median stable time: 13 weeks) and another 32% (16/50) SD-PSS managed to lower the dose or strength of topical steroid. Steroid-induced ocular hypertension happened in 5.26% (19/361) of the PSS patients., Conclusion: Young onset age, high IOP, and high iris depigmentation level during acute stage are indicators of steroid dependency in PSS patients. SD-PSS patients require more medical surveillance. Two percent ganciclovir and gradual decrement steroid combination therapy help with steroid withdrawal and minimize steroid use.

Objectives: Recent immunologic study of the adaptive immune repertoire in the subglottic airway demonstrated high-frequency T cell clones that do not overlap between individuals. However, the anatomic distribution and antigenic target of the T cell repertoire in the proximal airway mucosa remain unresolved., Methods: Single-cell RNA sequencing of matched scar and unaffected mucosa from idiopathic subglottic stenosis patients (iSGS, n = 32) was performed and compared with airway mucosa from healthy controls (n = 10). T cell receptor (TCR) sequences were interrogated via similarity network analysis to explore antigenic targets using the published algorithm: Grouping of Lymphocyte Interactions by Paratope Hotspots (GLIPH2)., Results: The mucosal T cell repertoire in healthy control airways consisted of highly expressed T cell clones conserved across anatomic subsites (trachea, bronchi, bronchioles, and lung). In iSGS, high-frequency clones were equally represented in both scar and adjacent non-scar tissue. Significant differences in repertoire structure between iSGS scar and unaffected mucosa was observed, driven by unique low-frequency clones. GLIPH2 results suggest low-frequency clones share targets between multiple iSGS patients., Conclusion: Healthy airway mucosa has a highly conserved T cell repertoire across multiple anatomic subsites. Similarly, iSGS patients have highly expressed T cell clones present in both scar and unaffected mucosa. iSGS airway scar possesses an abundance of less highly expanded clones with predicted antigen targets shared between patients. Interrogation of these shared motifs suggests abundant adaptive immunity to viral targets in iSGS airway scar. These results provide insight into disease pathogenesis and illuminate new treatment strategies in iSGS., Level of Evidence: NA Laryngoscope, 134:3245-3252, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

The rational design and synthesis of carbon nanocages with highly complex porous structures are continuously facing challenges in the development of high-performance supercapacitors (SCs). The electrochemical performance characteristics of electrodes rely on their compositions and fabrication methods. Here, we propose a universal and efficient approach for the in-situ synthesis of zeolitic imidazolate framework-8 (ZIF-8) on porous carbonized wood, where the selective utilization of hexacarbonyl molybdenum protects the structural integrity of the ZIF-8 precursor, preventing collapse during thermal treatment. The subsequent pyrolysis process leads to the formation of small-sized molybdenum carbide (MoC) which are embedded in carbon nanocages (CN). The composite electrode consists of MoC/CN embedded in a porous carbonized wood (PCW), and it shows area-specific capacity of 9.7F cm -2 and 9.4 F cm -2 at 5 mA cm -2 and 30 mA cm -2 , respectively. Subsequently, the symmetric supercapacitor, with two MoC/CN@PCW electrodes exhibits a areal specific capacitance of 2.7 F cm -2 at 5 mA cm -2 . Moreover, this supercapacitor maintains an capacitance retention rate of 98.5 % after 12,000 discharge cycles. The supercapacitor exhibits a power density of 6.5 mW cm -2 , resulting in an energy density of 0.864 mWh cm -2 . Therefore, the utilization of wood-based electrodes holds promise for energy storage systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Understanding of the mechanisms on bacteria-regulated mineral dissolution functions is important for further insight into mineral-microbe interactions. The functions of the two-component system have been studied. However, the molecular mechanisms involved in bacterial two-component system-mediated mineral dissolution are poorly understood. Here, the two-component regulatory system ResS/ResR in the mineral-solubilizing bacterium Pseudomonas pergaminensis F77 was characterized for its involvement in biotite dissolution. Strain F77 and the F77ΔresS, F77ΔresR, and F77ΔresS/R mutants were constructed and compared for the ResS/ResR system-mediated Fe and Al release from biotite in the medium and the mechanisms involved. After 3 days of incubation, the F77ΔresS, F77ΔresR, and F77ΔresS/R mutants significantly decreased the Fe and Al concentrations in the medium compared with F77. The F77ΔresS/R mutant had a greater impact on Fe and Al release from biotite than did the F77ΔresS or F77ΔresR mutant. The F77∆resS/R mutant exhibited significantly reduced Fe and Al concentrations by 21-61 % between 12 h and 48 h of incubation compared with F77. Significantly increased pH values and decreased cell counts on the mineral surfaces were found in the presence of the F77∆resS/R mutant compared with those in the presence of F77 between 12 h and 48 h of incubation. Metabolomic analysis revealed that the extracellular metabolites associated with biotite dissolution were downregulated in the F77ΔresS/R mutant. These downregulated metabolites included GDP-fucose, 20-carboxyleukotriene B4, PGP (16:1(9Z)/16:0), 3',5'-cyclic AMP, and a variety of acidic metabolites involved in carbohydrate, amino acid, and lipid metabolisms, glycan biosynthesis, and cellular community function. Furthermore, the expression levels of the genes involved in the production of these metabolites were downregulated in the F77ΔresS/R mutant compared with those in F77. Our findings suggested that the ResS/ResR system in F77 contributed to mineral dissolution by mediating the production of mineral-solubilizing related extracellular metabolites and bacterial adsorption on mineral surface., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: The capacity of presurgical image-defined risk factors (IDRFs) to predict secondary surgical outcomes in patients with neuroblastoma is controversial., Methods: The International Neuroblastoma Surgical Report Form (INSRF) was employed to retrospectively collect the clinical data of 53 patients diagnosed with neuroblastoma at our hospital from April 2014 to April 2020. IDRFs were identified at the time of diagnosis and reassessed during the course of neoadjuvant chemotherapy. Various statistical tests were used to evaluate the correlation between IDRFs and secondary surgical outcomes., Results: A total of 195 IDRFs were identified. Notably, by two courses of neoadjuvant chemotherapy, the number of "two body compartments," "intraspinal tumor extension," and "trachea-compressing" IDRFs decreased significantly (p = .001). The primary tumor volumes and the number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy, especially in "intraspinal tumor extension" IDRFs (p = .034). The median number of IDRF per patient was four (interquartile range [IQR]: 1-5) at diagnosis, which diminished to one (IQR: 1-3) subsequent to neoadjuvant chemotherapy. The presence of preoperative IDRFs was not associated with surgical complications (p = .286) or the extent of surgery (p = .188). However, the number of preoperative IDRFs linked to the extent of surgery (p = .002), not to operative complications (p = .669). Specifically, presurgery "renal vessel contact" IDRFs were predictive of surgical complications, while presurgery "infiltration of vital structures" IDRFs were associated with the extent of surgery., Conclusion: The number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy. The number and type of presurgery IDRFs may predict secondary surgical outcomes, surpassing the mere consideration of their presence or absence., (© 2024 Wiley Periodicals LLC.)

An increased risk of cardiometabolic disease accompanies persistent systemic inflammation. Yet, the innate and adaptive immune system features in persons who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states. Using well-characterized clinical cohorts, including participants with controlled HIV as a model for chronic inflammation and increased immune cell interactions, we show that circulating CD14 + monocytes complexed to CD3 + T cells are dynamic, biologically relevant, and increased in individuals with diabetes after adjusting for confounding factors. The complexes form functional immune synapses with increased expression of proinflammatory cytokines and greater glucose utilization. Furthermore, in persons with HIV, the CD3 + T-cell: CD14 + monocyte complexes had more HIV copies compared to matched CD14 + monocytes or CD4 + T cells alone. Our results demonstrate that circulating CD3 + T-cell:CD14 + monocyte pairs represent dynamic cellular interactions that may contribute to inflammation and cardiometabolic disease pathogenesis and may originate or be maintained, in part, by chronic viral infections. These findings provide a foundation for future studies investigating mechanisms linking T cellmonocyte cell-cell complexes to developing immune-mediated diseases, including HIV and diabetes., Competing Interests: Declaration of interests The authors have no competing interests.

Background: Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality, yet the etiology is poorly understood. We previously found that serum/glucocorticoid-regulated kinase 1 (SGK1) and epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel (ENaC)-dependent sodium entry into monocyte-derived antigen-presenting cells (APCs) and activation of NADPH oxidase, leading to the formation of isolevuglandins (IsoLGs) in SSBP. Whereas aldosterone via the mineralocorticoid receptor (MR) activates SGK1 leading to hypertension, our past findings indicate that levels of plasma aldosterone do not correlate with SSBP, and there is little to no MR expression in APCs. Thus, we hypothesized that cortisol acting via the glucocorticoid receptor (GR), not the MR in APCs mediates SGK1 actions to induce SSBP., Methods: We performed cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) analysis on peripheral blood mononuclear cells of humans rigorously phenotyped for SSBP using an inpatient salt loading/depletion protocol to determine expression of MR, GR, and SGK1 in immune cells. In additional experiments, we performed bulk transcriptomic analysis on isolated human monocytes following in vitro treatment with high salt from a separate cohort. We then measured urine and plasma cortisol, cortisone, renin, and aldosterone. Subsequently, we measured the association of these hormones with changes in systolic, diastolic, mean arterial pressure and pulse pressure as well as immune cell activation via IsoLG formation., Results: We found that myeloid APCs predominantly express the GR and SGK1 with no expression of the MR. Expression of the GR in APCs increased after salt loading and decreased with salt depletion in salt-sensitive but not salt-resistant people and was associated with increased expression of SGK1 . Moreover, we found that plasma and urine cortisol/cortisone but not aldosterone/renin correlated with SSBP and APCs activation via IsoLGs. We also found that cortisol negatively correlates with EETs., Conclusion: Our findings suggest that renal cortisol signaling via the GR but not the MR in APCs contributes to SSBP via cortisol. Urine and plasma cortisol may provide an important currently unavailable feasible diagnostic tool for SSBP. Moreover, cortisol-GR-SGK1-ENaC signaling pathway may provide treatment options for SSBP.

Mercury (Hg) contamination poses a global threat to the environment, given its elevated ecotoxicity. Herein, we employed the lepidopteran model insect, silkworm ( Bombyx mori ), to systematically investigate the toxic effects of Hg-stress across its growth and development, histomorphology, antioxidant enzyme activities, and transcriptome responses. High doses of Hg exposure induced evident poisoning symptoms, markedly impeding the growth of silkworm larvae and escalating mortality in a dose-dependent manner. Under Hg exposure, the histomorphology of both the midgut and fat body exhibited impairments. Carboxylesterase (CarE) activity was increased in both midgut and fat body tissues responding to Hg treatment. Conversely, glutathione S-transferase (GST) levels increased in the fat body but decreased in the midgut. The transcriptomic analysis revealed that the response induced by Hg stress involved multiple metabolism processes. Significantly differently expressed genes (DEGs) exhibited strong associations with oxidative phosphorylation, nutrient metabolisms, insect hormone biosynthesis, lysosome, ribosome biogenesis in eukaryotes, and ribosome pathways in the midgut or the fat body. The findings implied that exposure to Hg might induce the oxidative stress response, attempting to compensate for impaired metabolism. Concurrently, disruptions in nutrient metabolism and insect hormone activity might hinder growth and development, leading to immune dysfunction in silkworms. These insights significantly advance our theoretical understanding of the potential mechanisms underlying Hg toxicity in invertebrate organisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wen, Wang, Ji, Chen, Xiao, Lu, Jiang, Sheng, Nie and You.)

Background: This study aimed to investigate gestational age-specific hematological features in preterm infants with necrotizing enterocolitis (NEC) and identify predictive hematological biomarkers for surgical NEC., Methods: We conducted a retrospective study comparing gestational age (GA)-specific clinical data between medical NEC (m-NEC) and surgical NEC (s-NEC) subgroups, stratified by GA as <28 weeks, 28 ≤ GA < 32 weeks, and 32 ≤ GA < 37 weeks. Multivariate logistic analysis and receiver operating characteristic curve were used to identify the independent predictors of s-NEC., Results: In comparison to m-NEC at NEC onset, s-NEC infants exhibited the following findings: In GA < 28 weeks, s-NEC infants had lower platelet counts. In 28 ≤ GA < 32 weeks, lower absolute lymphocyte counts, and significant percent drop in platelets, lymphocytes, and monocytes were observed. In 32 ≤ GA < 37 weeks, lower absolute lymphocyte counts and significant percent drop in lymphocytes were found. Independent predictors were able to distinguish s-NEC from m-NEC. The area under the curve (AUC) for platelet counts in GA < 28 weeks was 0.880, while C-reactive protein in 28 ≤ GA < 32 weeks had an AUC of 0.889. The AUC for lymphocyte counts in 32 ≤ GA < 37 weeks was 0.892., Conclusion: This study identified hematological abnormalities in the development of NEC based on gestational age. Independent predictors may help clinicians distinguish surgical NEC from medical NEC., Impact: Necrotizing enterocolitis (NEC) patients with different gestational ages (GA) exhibit different hematological features and independent predictors of surgical NEC differ among different GAs. Our research made the current studies about peripheral hematological features with NEC more complete by analyzing peripheral data collected within 24 h of birth, at day 5-7, day 3-4, day 1-2 before NEC onset, at the time of NEC onset, day 1, day 2, day 3, day 4-5, day 6-7 after NEC onset. Our study is helpful to clinicians in developing a more detailed diagnostic strategy based on GA for the early identification of surgical NEC., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis., Methods: Restenosis and atherosclerosis rat models of type 2 diabetes (n  =  20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t-test and one-way analysis of variance were used for statistical analysis., Results: C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells., Conclusion: Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy that has consistently shown Wnt/β-catenin (canonical) signaling activation in various study populations. There are currently no targetable treatments for BRAF-wildtype ATC and a lack of effective treatment for BRAF V600E ATC. Our aim is to identify whether Wnt inhibitors could be potential therapeutic agents for ATC patients with limited treatment options., Methods: In this Institutional Review Board-approved study, we utilize a cohort of 32 ATCs and 20 non-neoplastic multinodular goiters (MNG). We also use 4 ATC spheroid cell lines (THJ-16T, THJ-21T, THJ-29T, and THJ-11T) and two primary patient-derived ATC organoid cultures (VWL-T5 and VWL-T60). Finally, we use a murine xenograft mouse model of ATC for in vivo treatment studies., Results: Using a large patient cohort, we demonstrate that this near-universal Wnt signaling activation is associated with ligand expression- rather than being mutationally-driven. We show that pyrvinium pamoate, a potent Wnt inhibitor, exhibits in vitro efficacy against both ATC cell lines and primary patient-derived ATC organoids VWL-T5 (p < 0.05) and VWL-T60 (p < 0.01) Finally, using a murine xenograft model of ATC, we show that pyrvinium significantly delays the growth of ATC tumors in THJ-16T (p < 0.005) and THJ-21T (p < 0.001)., Conclusions: We tested Wnt inhibitor treatment, both in vitro and in vivo, as a potential novel therapy for this highly lethal disease. Future large-scale studies utilizing multiple Wnt inhibitors will lay the foundation for the development of these novel therapies for patients with ATC., (© 2024. The Author(s).)

Hepatitis B is mostly a chronic, progressive disease that, if not treated promptly and effectively, can slowly progress to cirrhosis, liver failure, or hepatocellular carcinoma. Therefore, antiviral therapy, i.e., a "complete therapy" strategy, should be started as long as the virus is positive. Immediate antiviral treatment is not recommended for infected patients who are only in the immune-tolerant phase, mainly because of the milder conditions and poor antiviral therapy efficacy, according to antiviral indications in China's Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version). The relevant issues of why hepatitis B virus infection in the immune-tolerant phase is the last mile of "complete therapy," with an emphasis on the disease's characteristics and antiviral treatment strategies, are discussed here.

Combinatorial signaling by proinflammatory cytokines synergizes to exacerbate toxicity to cells and tissue injury during acute infections. To explore synergism at the gene-regulatory level, we investigated the dynamics of transcription and chromatin signaling in response to dual cytokines by integrating nascent RNA imaging mass spectrometry, RNA sequencing, amplification-independent mRNA quantification, assay for transposase-accessible chromatin using sequencing (ATAC-seq), and transcription factor profiling. Costimulation with interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNFα) synergistically induced a small subset of genes, including the chemokines CXCL9 , - 10 , and - 11 . Gene induction coincided with increased chromatin accessibility at non-coding regions enriched for p65 and STAT1 binding sites. To discover coactivator dependencies, we conducted a targeted chemogenomic screen of transcriptional inhibitors followed by modeling of inhibitor dose-response curves. These results identified high efficacy of either p300/CREB-binding protein (CBP) or bromodomain and extra-terminal (BET) bromodomain inhibitors to disrupt induction of synergy genes. Combination p300/CBP and BET bromodomain inhibition at half-maximal inhibitory concentrations (subIC 50 ) synergistically abrogated IFNγ/TNFα-induced chemokine gene and protein levels., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

In this study, the cadmium (Cd)-tolerant Ensifer adhaerens strain NER9 with quorum sensing (QS) systems (responsible for N-acyl homoserine lactone (AHL) production) was characterized for QS system-mediated Cd immobilization and the underlying mechanisms involved. Whole-genome sequence analysis revealed that strain NER9 contains the QS SinI/R and TraI/R systems. Strains NER9 and the NER9∆sinI/R, NER9∆traI/R, and NER9∆sinI/R-traI/R mutants were constructed and compared for QS SinI/R and TraI/R system-mediated Cd immobilization in the solution and the mechanisms involved. After 24 h of incubation, strain NER9 significantly decreased the Cd concentration in the Cd-contaminated solution compared with the NER9∆sinI/R, NER9∆traI/R, and NER9∆sinI/R-traI/R mutants. The NER9∆sinI/R mutant had a greater impact on Cd immobilization and a lower impact on the activities of AHLs than did the NER9∆traI/R mutant. The NER9∆sinI/R mutant had significantly greater Cd concentrations and lower cell wall- and exopolysaccharide (EPS)-adsorbed Cd contents than did strain NER9. Furthermore, the NER9∆sinI/R mutant presented a decrease in the number of functional groups interacting with Cd, compared with strain NER9. These results suggested that the SinI/R system in strain NER9 contributed to Cd immobilization by mediating cell wall- and EPS-adsorption in Cd-containing solution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The effects of heat moisture treatment (HMT) times on the physicochemical properties of three bean flours and their starch were analyzed. The colors of L*, b* and ΔE values increased significantly with time. The adzuki bean and pea flours showed better WAI and SP, and better gelation of starch at 2 h. The rheological properties of mixed HMT dough (3:7) exhibited the typical solid-like weak gel behavior. HMT had a significantly decreased on the pasting viscosity of bean flour starch with treated time. HMT caused the starch granules damage, but did not radically change the crystal type. FTIR results showed more proteins attached to the surface of starch granules, and the short-range molecular order decreased the DO at 2 h. In vitro digestibility inferred that RDS converted into SDS and RS. These results indicated that HMT significantly affected the digestibility and physicochemical properties of bean flours., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The incidence and mortality of cancer is ever-increasing, which poses a significant challengesto human health and a substantial economic burden to patients. At present, chemotherapy is still a primary treatment for various cancers. However, chemotherapy kills tumors but also induces the related side effects, whichadversely impacting patient quality of life and exacerbating suffering. Therefore, there is an urgent need for new and effective treatments that can control tumor growth while reducing the side effects for patients. Arterial chemoembolization has been attracted much attentionwhich attributed to the advantage of ability to embolize tumor vessels to block blood and nutrition supplies. Thus, to achieve local tumor control, it has become an effective means of local tumor control and has been widely used in clinical practice. Despite its efficacy, conventional arterial chemoembolization techniques, limited by embolization materials, have been associated with incomplete embolization and suboptimal drug delivery outcomes. Gradually, researchers have shifted their attention to a new type of embolic material called CalliSperes ® drug-eluting embolic bead (DEB). DEB can not only load high doses of drugs, but also has strong sustained drug release ability and good biocompatibility. The integration of DEBs with traditional arterial chemoembolization (DEB-TACE) promises targeted vascular embolization, mitigated tumor ischemia and hypoxia, and direct intravascular chemotherapy delivery. It can prevent cancer cell differentiation and accelerate their death, meanwhile, directly injecting chemotherapy drugs into the target blood vessels reduced the blood concentration of the whole body, thus reduced the toxic and side effects of chemotherapy. Furthermore, DEB-TACE's sustained drug release capability elevates local drug concentrations at the tumor site, amplifying its antitumor efficacy. Therefore, DEB-TACE has become a hot spot in clinical research worldwide. This review introduces the pathogenesis of solid tumors, the background of research and biological characteristics of DEB, and the action mechanism of DEB-TACE, as well as its clinical research in various solid tumors and future prospects. This review aims to provide new ideas for the treatment of DEB-TACE in various solid tumors., (© 2024. The Author(s).)

Existing grippers for unmanned aerial vehicle (UAV) manipulation have persistent challenges, highlighting a need for grippers that are soft, self-adaptive, self-contained, easy to control, and lightweight. Inspired by tendril plants, we propose a class of soft grippers that are voltage driven and based on winding deformation for self-adaptive grasping. We design two types of U-shaped soft eccentric circular tube actuators (UCTAs) and propose using the liquid-gas phase-transition mechanism to actuate UCTAs. Two types of UCTAs are separately cross-arranged to construct two types of soft grippers, forming self-contained systems that can be directly driven by voltage. One gripper inspired by tendril climbers can be used for delicate grasping, and the other gripper inspired by hook climbers can be used for strong grasping. These grippers are ideal for deployment in UAVs because of their self-adaptability, ease of control, and light weight, paving the way for UAVs to achieve powerful manipulation with low positioning accuracy, no complex grasping planning, self-adaptability, and multiple environments.

Rationale: Quantitative interstitial abnormalities (QIAs) are early measures of lung injury automatically detected on chest computed tomography scans. QIAs are associated with impaired respiratory health and share features with advanced lung diseases, but their biological underpinnings are not well understood. Objectives: To identify novel protein biomarkers of QIAs using high-throughput plasma proteomic panels within two multicenter cohorts. Methods: We measured the plasma proteomics of 4,383 participants in an older, ever-smoker cohort (COPDGene [Genetic Epidemiology of Chronic Obstructive Pulmonary Disease]) and 2,925 participants in a younger population cohort (CARDIA [Coronary Artery Disease Risk in Young Adults]) using the SomaLogic SomaScan assays. We measured QIAs using a local density histogram method. We assessed the associations between proteomic biomarker concentrations and QIAs using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, and study center (Benjamini-Hochberg false discovery rate-corrected P  ⩽ 0.05). Measurements and Main Results: In total, 852 proteins were significantly associated with QIAs in COPDGene and 185 in CARDIA. Of the 144 proteins that overlapped between COPDGene and CARDIA, all but one shared directionalities and magnitudes. These proteins were enriched for 49 Gene Ontology pathways, including biological processes in inflammatory response, cell adhesion, immune response, ERK1/2 regulation, and signaling; cellular components in extracellular regions; and molecular functions including calcium ion and heparin binding. Conclusions: We identified the proteomic biomarkers of QIAs in an older, smoking population with a higher prevalence of pulmonary disease and in a younger, healthier community cohort. These proteomics features may be markers of early precursors of advanced lung diseases.

Low pH (LpH) poses a significant challenge to the health, immune response, and growth of aquatic animals worldwide. Crayfish (Procambarus clarkii) is a globally farmed freshwater species with a remarkable adaptability to various environmental stressors. However, the effects of LpH stress on the microbiota and host metabolism in crayfish intestines remain poorly understood. In this study, integrated analyses of antioxidant enzyme activity, histopathological damage, 16S rRNA gene sequencing, and liquid chromatography-mass spectrometry (LC-MS) were performed to investigate the physiology, histopathology, microbiota, and metabolite changes in crayfish intestines exposed to LpH treatment. The results showed that LpH stress induced obvious changes in superoxide dismutase and catalase activities and histopathological alterations in crayfish intestines. Furthermore, 16S rRNA gene sequencing analysis revealed that exposure to LpH caused significant alterations in the diversity and composition of the crayfish intestinal microbiota at the phylum and genus levels. At the genus level, 14 genera including Bacilloplasma, Citrobacter, Shewanella, Vibrio, RsaHf231, Erysipelatoclostridium, Anaerorhabdus, Dysgonomonas, Flavobacterium, Tyzzerella, Brachymonas, Muribaculaceae, Propionivibrio, and Comamonas, exhibited significant differences in their relative abundances. The LC-MS analysis revealed 859 differentially expressed metabolites in crayfish intestines in response to LpH, including 363 and 496 upregulated and downregulated metabolites, respectively. These identified metabolites exhibited significant enrichment in 24 Kyoto Encyclopedia of Genes and Genomes pathways (p < 0.05), including seven and 17 upregulated and downregulated pathways, respectively. These pathways are mainly associated with energy and amino acid metabolism. Correlation analysis revealed a strong correlation between the metabolites and intestinal microbiota of crayfish during LpH treatment. These findings suggest that LpH may induce significant oxidative stress, intestinal tissue damage, disruption of intestinal microbiota homeostasis, and alterations in the metabolism in crayfish. These findings provide valuable insights into how the microbial and metabolic processes of crayfish intestines respond to LpH stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: High-density lipoprotein (HDL) has well-characterized anti-atherogenic cholesterol efflux and antioxidant functions. Another function of HDL uncharacterized in rheumatoid arthritis (RA) is its ability to transport microRNAs (miRNAs) between cells and thus alter cellular function. The study's purpose was to determine if HDL-miRNA cargo is altered and affects inflammation in RA., Methods: HDL-microRNAs were characterized in 30 RA and 30 control participants by next generation sequencing and quantitative polymerase chain reaction. The most abundant differentially expressed miRNA was evaluated further. The function of miR-1246 was assessed by miRNA mimics, antagomiRs, small interfering RNA knockdown, and luciferase assays. Monocyte-derived macrophages were treated with miR-1246-loaded HDL and unmodified HDL from RA and control participants to measure delivery of miR-1246 and its effect on interleukin-6 (IL-6)., Results: The most abundant miRNA on HDL was miR-1246; it was significantly enriched two-fold on HDL from RA versus control participants. HDL-mediated miR-1246 delivery to macrophages significantly increased IL6 expression 43-fold. miR-1246 delivery significantly decreased DUSP3 1.5-fold and DUSP3 small interfering RNA knockdown increased macrophage IL6 expression. Luciferase assay indicated DUSP3 is a direct target of miR-1246. Unmodified HDL from RA delivered 1.6-fold more miR-1246 versus control participant HDL. Unmodified HDL from both RA and control participants attenuated activated macrophage IL6 expression, but this effect was significantly blunted in RA so that IL6 expression was 3.4-fold higher after RA versus control HDL treatment., Conclusion: HDL-miR-1246 was increased in RA versus control participants and delivery of miR-1246 to macrophages increased IL-6 expression by targeting DUSP3. The altered HDL-miRNA cargo in RA blunted HDL's anti-inflammatory effect., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The choice of neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC) is controversial. This study aims to provide a basis for clinical treatment selection by establishing a predictive model for the efficacy of neoadjuvant immunochemotherapy (NICT)., Methods: A retrospective analysis of 30 patients was conducted, divided into Response and Non-response groups based on whether they achieved major pathological remission (MPR). Differences in genes and immune microenvironment between the two groups were analyzed through next-generation sequencing (NGS) and multiplex immunofluorescence (mIF). Variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves to establish a predictive model. An additional 48 patients were prospectively collected as a validation set to verify the model's effectiveness., Results: NGS suggested seven differential genes (ATM, ATR, BIVM-ERCC5, MAP3K1, PRG, RBM10, and TSHR) between the two groups (P < 0.05). mIF indicated significant differences in the quantity and location of CD3+, PD-L1+, CD3+PD-L1+, CD4+PD-1+, CD4+LAG-3+, CD8+LAG-3+, LAG-3+ between the two groups before treatment (P < 0.05). Dynamic mIF analysis also indicated that CD3+, CD8+, and CD20+ all increased after treatment in both groups, with a more significant increase in CD8+ and CD20+ in the Response group (P < 0.05), and a more significant decrease in PD-L1+ (P < 0.05). The three variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves: Tumor area PD-L1+ (AUC= 0.881), CD3+PD-L1+ (AUC= 0.833), and CD3+ (AUC= 0.826), and a predictive model was established. The model showed high performance in both the training set (AUC= 0.938) and the validation set (AUC= 0.832). Compared to the traditional CPS scoring criteria, the model showed significant improvements in accuracy (83.3% vs 70.8%), sensitivity (0.625 vs 0.312), and specificity (0.937 vs 0.906)., Conclusion: NICT treatment may exert anti-tumor effects by enriching immune cells and activating exhausted T cells. Tumor area CD3+, PD-L1+, and CD3+PD-L1+ are closely related to therapeutic efficacy. The model containing these three variables can accurately predict treatment outcomes, providing a reliable basis for the selection of neoadjuvant treatment plans., Competing Interests: Author CX was employed by the company Genecast Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yehan, Sheng, Hong, Jiayu, Jun, Juan, Min, Jiaxin, Shangzhi, Yi, Qifeng, Xuefeng, Wenwu, Xueyan, Yang and Zongyao.)

Breast cancer antiestrogen resistance 4 (BCAR4) has been suggested that can modulate cell behavior, resulting in tumorigenesis and chemoresistance. However, the underlying mechanisms of BCAR4 in trastuzumab resistance (TR) is still elusive. Here, we explored the function and the underlying mechanism of BCAR4 involving in TR. We found that BCAR4 is significantly upregulated in trastuzumab-resistant BC cells. Knockdown of BCAR4 could sensitize the BC cells to trastuzumab and suppress epithelial-mesenchymal transition (EMT). Mechanically, BCAR4 promotes yes-associated protein 1 (YAP1) expression by competitively sponging miR-665, to activated TGF-β signaling. Reciprocally, YAP1 could occupy the BCAR4 promoter to enhance its transcription, suggesting that there exists a positive feedback regulation between YAP1 and BCAR4. Targeting the BCAR4/miR-665/YAP1 axis may provide a novel insight of therapeutic approaches for TR in BC., (© 2024 Federation of American Societies for Experimental Biology.)

Cutaneous candidiasis, caused by Candida albicans , is a severe and frustrating condition, and finding effective treatments can be challenging. Therefore, the development of farnesol-loaded nanoparticles is an exciting breakthrough. Ethosomes are a novel transdermal drug delivery carrier that incorporates a certain concentration (10-45%) of alcohols into lipid vesicles, resulting in improved permeability and encapsulation rates compared to conventional liposomes. Farnesol is a quorum-sensing molecule involved in morphogenesis regulation in C. albicans , and these ethosomes offer a promising new approach to treating this common fungal infection. This study develops the formulation of farnesol-loaded ethosomes (farnesol-ethosomes) and assesses applications in treating cutaneous candidiasis induced by C. albicans in vitro and in vivo . Farnesol-ethosomes were successfully developed by ethanol injection method. Therapeutic properties of farnesol-ethosomes, such as particle size, zeta potential, and morphology, were well characterized. According to the results, farnesol-ethosomes demonstrated an increased inhibition effect on cells' growth and biofilm formation in C. albicans . In Animal infection models, treating farnesol-ethosomes by transdermal administration effectively relieved symptoms caused by cutaneous candidiasis and reduced fungal burdens in quantity. We also observed that ethosomes significantly enhanced drug delivery efficacy in vitro and in vivo . These results indicate that farnesol-ethosomes can provide future promising roles in curing cutaneous candidiasis., Importance: Cutaneous candidiasis attributed to Candida infection is a prevalent condition that impacts individuals of all age groups. As a type of microbial community, biofilms confer benefits to host infections and mitigate the clinical effects of antifungal treatments. In C. albicans , the yeast-to-hypha transition and biofilm formation are effectively suppressed by farnesol through its modulation of multiple signaling pathway. However, the characteristics of farnesol such as hydrophobicity, volatility, degradability, and instability in various conditions can impose limitations on its effectiveness. Nanotechnology holds the potential to enhance the efficiency and utilization of this molecule. Treatment of farnesol-ethosomes by transdermal administration demonstrated a very remarkable therapeutic effect against C. albicans in infection model of cutaneous candidiasis in mice. Many patients suffering fungal skin infection will benefit from this study., Competing Interests: The authors declare no conflict of interest.