A probabilistic approach for assessing the mechanical performance of intertrochanteric fracture stabilized with proximal femoral nail antirotation.

Maintaining post-operative mechanical stability is crucial for successfully healing intertrochanteric fractures treated with the Proximal Femoral Nail Antirotation (PFNA) system. This stability is primarily dependent on the bone mineral density (BMD) and strain on the fracture. Current PFNA failure analyses often overlook the uncertainties related to BMD and body weight (BW). Therefore, this study aimed to develop a probabilistic model using finite element modeling and engineering reliability analysis to assess the post-operative performance of PFNA under various physiological loading conditions. The model predictions were validated through a series of experimental test. The results revealed a negative nonlinear relationship between the BMD and compressive strain. Conversely, the BW was positively and linearly correlated with the compressive strain. Importantly, the compressive strain was more sensitive to BW than to BMD when the BMD exceeded 0.6 g/cm3. Potential trabecular bone compression failure is also indicated if BMD is equal to or below 0.15 g/cm3 and BW increases to approximately 2.5 times the normal or higher. This study emphasizes that variations in the BMD significantly affect the probability of failure of a PFNA system. Thus, careful planning of post-operative physical therapy is essential. For patients aged > 50 years restrictions on high-intensity activities are advised, while limiting strenuous movements is recommended for those aged > 65 years.

Effect of coffee, tea and alcohol intake on circulating inflammatory cytokines: a two sample-Mendelian randomization study.

BACKGROUND: Despite the abundance of research examining the effects of coffee, tea, and alcohol on inflammatory diseases, there is a notable absence of conclusive evidence regarding their direct causal influence on circulating inflammatory cytokines. Previous studies have primarily concentrated on established cytokines, neglecting the potential impact of beverage consumption on lesser-studied but equally important cytokines. METHODS: Information regarding the consumption of coffee, tea, and alcohol was collected from the UK Biobank, with sample sizes of 428,860, 447,485, and 462,346 individuals, respectively. Data on 41 inflammatory cytokines were obtained from summary statistics of 8293 healthy participants from Finnish cohorts. RESULTS: The consumption of coffee was found to be potentially associated with decreased levels of Macrophage colony-stimulating factor (ß = -0.57, 95% CI -1.06 ~ -0.08; p = 0.022) and Stem cell growth factor beta (ß = -0.64, 95% CI -1.16 ~ -0.12; p = 0.016), as well as an increase in TNF-related apoptosis-inducing ligand (ß = 0.43, 95% CI 0.06 ~ 0.8; p = 0.023) levels. Conversely, tea intake was potentially correlated with a reduction in Interleukin-8 (ß = -0.45, 95% CI -0.9 ~ 0; p = 0.045) levels. Moreover, our results indicated an association between alcohol consumption and decreased levels of Regulated on Activation, Normal T Cell Expressed and Secreted (ß = -0.24, 95% CI -0.48 ~ 0; p = 0.047), as well as an increase in Stem cell factor (ß = 0.17, 95% CI 0.02 ~ 0.31; p = 0.023) and Stromal cell-derived factor-1 alpha (ß = 0.20, 95% CI 0.04 ~ 0.36; p = 0.013). CONCLUSION: Revealing the interactions between beverage consumption and various inflammatory cytokines may lead to the discovery of novel therapeutic targets, thereby facilitating dietary interventions to complement clinical disease treatments.

The performance of OPC and OPC3 water models in predictions of 2D structures under nanoconfinement.

Nanoconfined water plays an important role in broad fields of science and engineering. Classical molecular dynamics (MD) simulations have been widely used to investigate water phases under nanoconfinement. The key ingredient of MD is the force field. In this study, we systematically investigated the performance of a recently introduced family of globally optimal water models, OPC and OPC3, and TIP4P/2005 in describing nanoconfined two-dimensional (2D) water ice. Our studies show that the melting points of the monolayer square ice (MSI) of all three water models are higher than the melting points of the corresponding bulk ice Ih. Under the same conditions, the melting points of MSI of OPC and TIP4P/2005 are the same and are ∼90 K lower than that of the OPC3 water model. In addition, we show that OPC and TIP4P/2005 water models are able to form a bilayer AA-stacked structure and a trilayer AAA-stacked structure, which are not the cases for the OPC3 model. Considering the available experimental data and first-principles simulations, we consider the OPC water model as a potential water model for 2D water ice MD studies.

Prevention of Hypercholesterolemia with "Liposomes in Microspheres" Composite Carriers: A Promising Approach for Intestinal-Targeted Oral Delivery of Astaxanthin.

Cardiovascular diseases are caused by hypercholesterolemia. Astaxanthin (AST) has been reported to exhibit antioxidant and anti-inflammatory properties. However, its bioavailability is poor because of low solubility and instability. In order to improve the bioavailability of AST, we developed an intestinal-responsive composite carrier termed as "liposomes in micropheres" incorporating N-succinyl-chitosan (NSC)-poly(ethylene glycol) (PEG) liposomes that functionalized by neonatal Fc receptors (FcRn) into hydrogels of sodium alginate (SA) and carboxymethyl chitosan (CMCS). In the AST NSC/HSA-PEG liposomes@SA/CMCS microspheres, the AST's encapsulation efficiency (EE) was 96.26% (w/w) and its loading capacity (LC) was 6.47% (w/w). AST NSC/HSA-PEG liposomes had stability in the gastric conditions and achieved long-term release of AST in intestinal conditions. Then, AST NSC/HSA-PEG liposomes@SA/CMCS bind to intestinal epithelial cell targets by the neonatal Fc receptor. In vitro permeation studies show that there was a 4-fold increase of AST NSC/HSA-PEG liposomes@SA/CMCS in AST permeation across the intestinal epithelium. Subsequent in vivo experiments demonstrated that the composite carrier exhibited a remarkable mucoadhesive capacity, allowing for extended intestinal retention of up to 12 h, and it displayed deep penetration through the mucus layer, efficiently entering the intestinal villi epithelial cells, and enhancing the absorption of AST and its bioavailability in vivo. And oral administration of AST NSC/HSA-PEG liposomes@SA/CMCS could effectively prevent hypercholesterolemia caused by a high-fat, high-cholesterol diet (HFHCD). These advancements highlight the potential of NSC/HSA-PEG liposomes@SA/CMCS composite carriers for targeted and oral uptake of hydrophobic bioactives.

Mechanistic insight into the competition between interfacial and bulk reactions in microdroplets through N2O5 ammonolysis and hydrolysis.

Reactive uptake of dinitrogen pentaoxide (N2O5) into aqueous aerosols is a major loss channel for NOx in the troposphere; however, a quantitative understanding of the uptake mechanism is lacking. Herein, a computational chemistry strategy is developed employing high-level quantum chemical methods; the method offers detailed molecular insight into the hydrolysis and ammonolysis mechanisms of N2O5 in microdroplets. Specifically, our calculations estimate the bulk and interfacial hydrolysis rates to be (2.3 ± 1.6) × 10-3 and (6.3 ± 4.2) × 10-7 ns-1, respectively, and ammonolysis competes with hydrolysis at NH3 concentrations above 1.9 × 10-4 mol L-1. The slow interfacial hydrolysis rate suggests that interfacial processes have negligible effect on the hydrolysis of N2O5 in liquid water. In contrast, N2O5 ammonolysis in liquid water is dominated by interfacial processes due to the high interfacial ammonolysis rate. Our findings and strategy are applicable to high-chemical complexity microdroplets.

Identification and genetic characterization of a recently identified enterovirus C116 in China.

Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.

DNA polymerase iota promotes EMT and metastasis of esophageal squamous cell carcinoma by interacting with USP7 to stabilize HIF-1α.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancer types, with a low 5-year survival rate of ~20%. Our prior research has suggested that DNA Polymerase iota (Pol ι), a member of Y-family DNA polymerase, plays a crucial role in the invasion and metastasis of ESCC. However, the underlying mechanism is not well understood. In this study, we utilized ChIP-PCR and luciferase reporter assays to investigate the binding of HIF-1α to the promoter of the Pol ι gene. Transwell, wound healing, and mouse models were employed to assess the impact of Pol ι and HIF-1α on the motility of ESCC cells. Co-immunoprecipitation and Western blot were carried out to explore the interaction between Pol ι and HIF-1α, while qRT-PCR and Western blot were conducted to confirm the regulation of Pol ι and HIF-1α on their downstream targets. Our results demonstrate that HIF-1α activates the transcription of the Pol ι gene in ESCC cells under hypoxic conditions. Furthermore, the knockdown of Pol ι impeded HIF-1α-induced invasion and metastasis. Additionally, we found that Pol ι regulates the expression of genes involved in epithelial-mesenchymal transition (EMT) and initiates EMT through the stabilization of HIF-1α. Mechanistically, Pol ι maintains the protein stability of HIF-1α by recruiting USP7 to mediate the deubiquitination of HIF-1α, with the residues 446-578 of Pol being crucial for the interaction between Pol ι and USP7. Collectively, our findings unveil a novel feedforward molecular axis of HIF-1α- Pol ι -USP7 in ESCC that contributes to ESCC metastasis. Hence, our results present an attractive target for intervention in ESCC.

The chemical and biological characteristics of fatty acid esters of hydroxyl fatty acids.

With the continuous advancements in detection methods and the exploration of unknown substances, an increasing number of bioactive compounds are being discovered. Fatty acid esters of hydroxyl fatty acids (FAHFAs), a class of endogenous lipids found in 2014, exhibit various physiological activities, such as improving glucose tolerance and insulin sensitivity, stimulating insulin secretion, and demonstrating broad anti-inflammatory effects. Moreover, some FAHFAs are closely linked to intestinal health and can serve as potential biomarkers for gut health. Various FAHFAs have been observed in food, including palmitic acid esters of hydroxy stearic acids (PAHSA), oleic acid esters of hydroxy stearic acids (OAHSA), linoleic acid esters of hydroxy linoleic acid (LAHLA). As a type of lipid regularly consumed in the daily diet, it is highly important to ascertain the types and quantities of FAHFAs present in the diet. This article, based on existing research, provides a review of the analysis methods for FAHFAs, particularly focusing on the separation of chiral isomers. It also summarizes the sources and contents of dietary FAHFAs, emphasizing their bioavailability and impact on the gut. Understanding the beneficial effects of these lipids in the diet can serve as a valuable reference for the development of specific functional foods.

All-Inside Anterior Cruciate Ligament Reconstruction Had Clinical Outcome Similar to the Transtibial Technique Except for Improved Side-to-Side Difference and Tegner Activity Scale: A Systematic Review and Meta-Analysis.

PURPOSE: To compare clinical outcomes of the all-inside technique with the transtibial technique in anterior cruciate ligament reconstruction based on available literature on this topic. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, we conducted a systematic search for randomized controlled trials and cohort studies. Our comprehensive search encompassed PubMed, Embase, Cochrane Library, and Web of Science. We included randomized controlled trials (RCTs) and cohort studies that compared the 2 techniques with a minimal 1-year follow-up. Two independent authors assessed RCTs using the risk of bias tool developed by the Cochrane Collaboration and evaluated the quality of cohort studies using the Newcastle-Ottawa Scale for Assessing the Quality of Nonrandomized Comparative Trials. The subjective and objective outcomes, complications, and graft failure were obtained. R software was used to perform the analysis. RESULTS: The present analysis enrolled 9 RCTs (n = 687) and 11 cohort studies (n = 910). After a minimal 1-year follow-up in RCTs, functional outcomes such as International Knee Documentation Committee (IKDC) subjective score, Lysholm score, Tegner activity scale, Knee Society Score, and hop test were found to be similar between 2 techniques. The laxity outcomes, including the IKDC objective grade and pivot-shift test, were suggested to be comparable. There was a significant difference favoring the transtibial technique in terms of side-to-side difference (P = .04; 95% confidence interval [CI], 0.08-0.90). The pooled data from cohort studies indicated equivalent results in terms of IKDC subjective score, Lysholm score, side-to-side difference, IKDC objective grade, complications, and graft failure, with the exception of statistical difference in the Tegner activity scale (P = .03; 95% CI, -0.50 to -0.04). CONCLUSIONS: Our findings suggest that there is no difference in most outcome scores between the all-inside and transtibial techniques for anterior cruciate ligament reconstruction. There are statistically significant differences in side-to-side difference and Tegner activity scale favoring the all-inside technique. LEVEL OF EVIDENCE: Level IV, meta-analysis of Level I to IV studies.

Mathematical definition and rules of the splitting/merging patterns in bundles of human peripheral nerve segment.

Accurately measuring the spatial extension distance of nerve bundles in completing a split/merge is impossible because no clear mathematical definition exists for the starting and ending positions in nerve-bundle splitting/merging. We manually count the number of nerve-bundle splits/merges in long nerve segments, which is labor-intensive, inefficient, and prone to counting errors. Currently, the mathematics are unclear for the nerve-bundle diameter before and after splitting/merging. This paper explores these problems and proposes nerve-bundle splitting/merging rules. Based on the method of defining the beginning and ending positions of nerve-bundle splitting/merging, we explored the mathematical law of equivalent diameter of nerve bundles before and after splitting/merging. The experimental results revealed that the moving average of circularity of nerve bundle accurately defines the beginning and ending positions of nerve-bundle splitting/merging. The diameter of the nerve bundles before and after split/merge approximately conforms to the principles of the Da Vinci formula. The proposed automatic counting algorithm based on centroid offset matching obtains the number of split/merged nerve bundles in the sequence scan images with 100 % accuracy. The mathematical definition of the starting and ending positions of nerve-bundle splitting/merging proposed in this paper is accurate and strict and is the foundation of subsequent research. The proposed automatic counting algorithm based on centroid offset matching (ACA-COM) can accurately and efficiently count the number of times the nerve bundles split and merge in sequential images. The mathematical law satisfied by the diameter of the nerve bundles before and after splitting/merging reflects that the nerve bundles tend to have better capability to resist breaking.

Development and application of mass spectrometric molecular networking for analyzing the ingredients of areca nut.

Areca nut (Areca catechu L.) is commonly consumed as a chewing food in the Asian region. However, the investigations into the components of areca nut are limited. In this study, we have developed an approach that combines mass spectrometry with feature-based molecular network to explore the chemical characteristics of the areca nut. In comparison to the conventional method, this technique demonstrates a superior capability in annotating unknown compounds present in areca nut. We annotated a total of 52 compounds, including one potential previously unreported alkaloid, one carbohydrate, and one phenol and confirmed the presence of 7 of them by comparing with commercial standards. The validated method was used to evaluate chemical features of areca nut at different growth stages, annotating 25 compounds as potential biomarkers for distinguishing areca nut growth stages. Therefore, this approach offers a rapid and accurate method for the component analysis of areca nut.

Meningitis in neonate caused by Mycoplasma hominis: A case report.

Background: Mycoplasma hominis (M. hominis) commonly colonizes the genitourinary tract of adult women and may result in neonatal meningitis through vertical transmission. Although there are few case reports, if the treatment is not conducted timely, the disease progresses rapidly, which may lead to serious complications and a poor prognosis. Case presentation: In the present study, a 10-day-old full-term neonate who presented with fever as the initial symptom and was eventually diagnosed with meningitis caused by M. hominis was reported. In the present case, the pathogen was not detected during the initial routine investigations, and the therapeutic effects of empiric antibiotic therapy were poor. Metagenomic next-generation sequencing (mNGS) in the cerebrospinal fluid (CSF) was conducted with the detection of M. hominis, and the antibiotics were adjusted to moxifloxacin combined with doxycycline. The clinical symptoms of the pediatric patient disappeared with an improvement in related laboratory results. Conclusion: It was difficult to detect M. hominis by routine bacterial culture. Therefore, M. hominis infection should be checked for in children with meningitis who had a negative result in CSF culture and poor therapeutic effects of empirical medication. mNGS in CSF should be conducted as soon as possible, and sensitive antibiotics should be administered in time to reduce the incidence of complications and improve the prognosis.

SpecLipIDA: a pseudotargeted lipidomics approach for polyunsaturated fatty acids in milk.

Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), play an important role in the nutritional value of milk lipids. However, a comprehensive analysis of PUFAs and their esters in milk is still scarce. In this study, we developed a novel pseudotargeted lipidomics approach, named SpecLipIDA, for determining PUFA lipids in milk. Triglycerides (TGs) and phospholipids (PLs) were separated using NH2 cartridges, and mass spectrometry data in the information-dependent acquisition (IDA) mode were preprocessed by MS-DIAL, leading to improved identification in subsequent targeted analysis. The target matching algorithm, based on specific lipid cleavage patterns, demonstrated enhanced identification of PUFA lipids compared to the lipid annotations provided by MS-DIAL and GNPS. The approach was applied to identify PUFA lipids in various milk samples, resulting in the detection of a total of 115 PUFA lipids. The results revealed distinct differences in PUFA lipids among different samples, with 44 PUFA lipids significantly contributing to these differences. Our study indicated that SpecLipIDA is an efficient method for rapidly and specifically screening PUFA lipids.

Simultaneous decarbonization and phosphorus removal by Tetrasphaera elongata with glucose as carbon source under aerobic conditions.

Previous researches have recognized the vital role of Tetrasphaera elongata in enhanced biological phosphorus removal systems, but the underlying mechanisms remain under-investigated. To address this issue, this study investigated the metabolic characteristics of Tetrasphaera elongata when utilizing glucose as the sole carbon source. Results showed under aerobic conditions, Tetrasphaera elongata exhibited a glucose uptake rate of 136.6 mg/(L·h) and a corresponding phosphorus removal rate of 8.6 mg P/(L·h). Upregulations of genes associated with the glycolytic pathway and oxidative phosphorylation were observed. Noteworthily, the genes encoding the two-component sensor histidine kinase and response regulator transcription factor exhibited a remarkable 28.3 and 27.4-fold increase compared with the group without glucose. Since these genes play a pivotal role in phosphate-specific transport systems, collectively, these findings shed light on a potential mechanism for simultaneous decarbonization and phosphorus removal by Tetrasphaera elongata under aerobic conditions, providing fresh insights into phosphorus removal from wastewaters.

Association between gut microbiota and seven gastrointestinal diseases: A Mendelian randomized study.

BACKGROUND: Observational research has shed light on the ability of gut microbes to influence the onset and progression of gastrointestinal diseases. The causal relationships between specific gut microbiomes and various gastrointestinal conditions, however, remain unknown. METHODS: We investigated the relationship between gut microbiota and seven specific gastrointestinal disorders using a robust two-sample Mendelian randomization (MR) approach. The inverse variance-weighted (IVW) method was used as the primary analysis tool in our study. Furthermore, we conducted multiple sensitivity analyses to strengthen the robustness of our findings and ensure the reliability of the IVW method. RESULTS: Our research has discovered significant links between the composition of gut microbiota and a variety of gastrointestinal ailments. We found compelling links between 13 gut microbiota and fatty liver, four gut microbiota and cirrhosis, eight gut microbiota and hepatocellular carcinoma, four gut microbiota and cholelithiasis, 12 gut microbiota and acute pancreatitis, eight gut microbiota and chronic pancreatitis, and 11 gut microbiota and pancreatic cancer. These findings shed light on the intricate relationship between gut microbes and the emergence of these specific gastrointestinal conditions. CONCLUSIONS: The findings of this extensive study not only validate the potential role of specific gut microbiota in gastrointestinal diseases, but also fill a critical gap in previous research. The discovery of these specific gut microbiota is a significant step forward because they may serve as novel and promising biomarkers for both the prevention and treatment of gastrointestinal conditions.

Using Mesoporous Silica-Based Dual Biomimetic Nano-Erythrocytes for an Improved Antitumor Effect.

The nano-delivery system with a dual biomimetic effect can penetrate deeper in tumor microenvironments (TMEs) and release sufficient antitumor drugs, which has attracted much attention. In this study, we synthesized erythrocyte-like mesoporous silica nanoparticles (EMSNs) as the core loaded with doxorubicin (DOX) and coated them with calcium phosphate (CaP) and erythrocyte membrane (EM) to obtain DOX/EsPMs. The transmission electron microscopy (TEM), fluorescent co-localization and protein bands of SDS-PAGE were used to confirm the complete fabrication of EsPMs. The EsPMs with erythrocyte-like shape exhibited superior penetration ability in in vitro diffusion and tumor-sphere penetration experiments. Intracellular Ca2+ and ROS detection experiments showed that the CaP membranes of EsPMs with pH-sensitivity could provide Ca2+ continuously to induce reactive oxide species' (ROS) generation in the TME. The EM as a perfect "camouflaged clothing" which could confuse macrophagocytes into prolonging blood circulation. Hemolysis and non-specific protein adsorption tests proved the desirable biocompatibility of EsPMs. An in vivo pharmacodynamics evaluation showed that the DOX/EsPMs group had a satisfactory tumor-inhibition effect. These advantages of the nano-erythrocytes suggest that by modifying the existing materials to construct a nano-delivery system, nanoparticles will achieve a biomimetic effect from both their structure and function with a facilitated and sufficient drug release profile, which is of great significance for antitumor therapy.

[Characterization and phylogenetic analysis of complete chloroplast genome of cultivated Qinan agarwood].

"Tangjie" leaves of cultivated Qinan agarwood were used to obtain the complete chloroplast genome using high-throughput sequencing technology. Combined with 12 chloroplast genomes of Aquilaria species downloaded from NCBI, bioinformatics method was employed to determine the chloroplast genome characteristics and phylogenetic relationships. The results showed that the chloroplast genome sequence length of cultivated Qinan agarwood "Tangjie" leaves was 174 909 bp with a GC content of 36.7%. A total of 136 genes were annotated, including 90 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Sequence repeat analysis detected 80 simple sequence repeats(SSRs) and 124 long sequence repeats, with most SSRs composed of A and T bases. Codon preference analysis revealed that AUU was the most frequently used codon, and codons with A and U endings were preferred. Comparative analysis of Aquilaria chloroplast genomes showed relative conservation of the IR region boundaries and identified five highly variable regions: trnD-trnY, trnT-trnL, trnF-ndhJ, petA-cemA, and rpl32, which could serve as potential DNA barcodes specific to the Aquilaria genus. Selection pressure analysis indicated positive selection in the rbcL, rps11, and rpl32 genes. Phylogenetic analysis revealed that cultivated Qinan agarwood "Tangjie" and Aquilaria agallocha clustered together(100% support), supporting the Chinese origin of Qinan agarwood from Aquilaria agallocha. The chloroplast genome data obtained in this study provide a foundation for studying the genetic diversity of cultivated Qinan agarwood and molecular identification of the Aquilaria genus.

Protonated and deprotonated vanadyl imidazole tartrates for the mimics of the vanadium coordination in the FeV-cofactor of V-nitrogenase.

Chiral imidazole-based oxidovanadium tartrates (H2im)2[Δ,Λ-VIV2O2(R,R-H2tart)(R,R-tart)(Him)2]·Him (1, H4tart = tartaric acid, Him = imidazole) and [Λ,Λ-VIV2O2(R,R-tart)(Him)6]·4H2O (2) and their corresponding enantiomers (H2im)2[Λ,Δ-VIV2O2(S,S-H2tart)(S,S-tart)(Him)2]·Him (3) and [Δ,Δ-VIV2O2(S,S-tart)(Him)6]·4H2O (4) were obtained in alkaline solutions. Interestingly, the tartrates chelate with vanadium bidentately through α-alkoxy/α-hydroxy and α-carboxy groups and imidazole coordinates monodentately through nitrogen atom. It is worth noting that complexes 1 and 3 contain both protonated α-hydroxy and deprotonated α-alkoxy groups simultaneously, which have short V-Oα-alkoxy distances [1.976(4)av Å in 1-4] and long V-Oα-hydroxy distances [2.237(3)av Å in 1 and 2.230(2)av Å in 3]. There is an interesting strong intramolecular hydrogen bond [O(11)⋯O(1) 2.731(5) Å] between the two parts in 1 and 3. The protonated V-O distances are closer to the average bond distance in reported FeV-cofactors (FeV-cos, V-Oα-alkoxy 2.156av Å) in VFe proteins, which corresponds to the feasible protonation of coordinated α-hydroxy in R-homocitrate in V-nitrogenase, showing the homocitrate in the mechanistic model for nitrogen reduction as a secondary proton donor. Furthermore, vibrational circular dichroism (VCD) and IR spectra of 1-4 pointed out the disparity between the characteristic vibrations of the C-O and C-OH groups clearly. EPR experiment and theoretical calculations support +4 oxidation states for vanadium in 1-4. Solution 13C {1H} NMR spectra and CV analyses exhibited the solution properties for 1 and 2, respectively, which indicates that there should be a rapid exchange equilibrium between the protonated and deprotonated species in solutions.

The Initial Efficacy of Comprehensive Treatment of External Treatment of Traditional Chinese Medicine on Acute Mastitis During Lactation and its Influence on Patients' Symptoms.

Objective: To evaluate the initial efficacy of comprehensive treatment of external treatment of traditional Chinese medicine in the therapy of acute mastitis during lactation and its influence on sufferers' symptoms. Methods: From January 2021 to January 2023, a retrospective analysis was performed on 100 sufferers with acute mastitis during lactation who were received in our hospital as the study objects. Divided them into a control group (n = 50) and an observation group (n = 50). Among them, the control one was received in 50% magnesium sulfate for moist heat compress, and the observation one was treated with comprehensive external therapy of traditional Chinese medicine. After different treatment measures were carried out in the 2 groups, the total effective ratio of clinical therapy, excellent and good rates of lactation, quality of life measurements, pain scores before and after treatment, and TCM symptom points at pre-therapy and post-therapy, negative emotion scores at pre-therapy and post-therapy related to patients were analyzed. Results: (1) In the data comparison of the total effective ratio of clinical therapy between the 2 groups of sufferers after therapy, the data in the observation one were greater than the control one, and the distinction was obvious, with P < .05. (2) In the data comparison of the excellent and good lactation rate between the 2 groups of sufferers at post-therapy, the data in observation one were greater than the control one, and the distinction was obvious, with P < .05. (3) In the data comparison of quality of life measurements between the 2 groups of sufferers at post-therapy, the data in the observation one were greater than the control one, and the distinction was obvious, with P < .05. (4) Before treatment, it had no obvious distinction in the pain scores between the 2 groups, with P > .05; in the data comparison of the pain points between the 2 groups after therapy, the data in observation one were less than the control one, and the distinction was obvious, with P < .05. (5) Before therapy, it had no obvious distinction in TCM symptom points between the 2 groups, with P > .05; in the data comparison of TCM symptom points between the 2 groups after therapy, the data in the observation one were less than the control one, and the distinction was obvious, with P < .05. (6) Before therapy, it had no obvious distinction in negative emotion points between the 2 groups, with P > .05; in the data comparison of negative emotion scores between the 2 groups of sufferers at post-therapy, the data in the observation one were less than those in the control one, and the distinction was obvious, with P < .05. Conclusion: The comprehensive therapy of TCM external treatment for acute mastitis during lactation has a significant therapeutic effect, which is conducive to improving the clinical symptoms of sufferers as soon as possible and at the same time, greatly improving the life quality of sufferers and improving their negative emotions, which can relieve the pain of sufferers and promote the recovery of the sufferers.

Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. METHODS: Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. RESULTS: F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. CONCLUSIONS: Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.