Experiments Validated the Development of Zebrafish Embryos and Toxicological Mechanism of Borneols in Perinatal Period.

BACKGROUND: Studies have confirmed that high dose borneol has perinatal toxicity and has a certain effect on embryonic development. However, there is little about the effect of borneol on the development of zebrafish embryos. Therefore, we compared the effects of D-borneol, L-borneol and synthetic borneol on the growth and development of zebrafish embryos, and predicted the possible mechanism of perinatal toxicity. METHODS: The embryonic mortality rate, hatching rate, and heart rate of each group were recorded at 48 hpf to compare the effects of borneols on the development of zebrafish embryos. Network pharmacology and molecular docking technology were used to predict the possible mechanism of perinatal toxicity. RESULTS: We found that borneols increased the mortality at 24 and 48 hpf, inhibited the autonomous movement behavior at 24 hpf, and affected the hatching rate and heart rate at 48 hpf. Network pharmacology analysis showed that borneols had the same toxic targets in the perinatal period and were involved in regulating perinatal toxicity by regulating pathways in cancer, chemical carcinogenesis-receptor activation, PI3K-Akt and others. Molecular docking showed that the binding activity of the active ingredients and the core target was at a medium level, and the binding activity of the borneols active ingredients and the core target was not much different. CONCLUSION: Three kinds of borneol on the development of zebrafish embryos were different. The toxicity of L-borneol was the lowest. The mechanisms of perinatal toxicity were related to inflammation, apoptosis, cell cycle and growth, differentiation and reproduction.

Interfacially Self-Assembled Mutifunctional Protein Thin Films for Accelerated Wound Healing.

The design of mutifunctional protein films for large-area spatially ordered arrays of functional components holds great promise in the field of biomedical applications. Herein, interfacial electrostatic self-assembly was employed to construct a large-scale protein thin film by inducing electrostatic interactions between three bovine serum albumin (BSA)-coated nanoclusters and cetyltrimethylammonium bromide (CTAB), leading to their spontaneous organization and uniform distribution at the oil-water interface. This protein film demonstrated excellent multienzyme functions, high antibacterial activity, and pH-responsive drug release capability. Therefore, it can accelerate the wound closure process through a synergistic effect that includes reducing local blood glucose levels, regulating cellular oxidative stress, eradicating bacteria, and promoting cell proliferation.

Development of an hollow fiber solid phase microextraction method for the analysis of unbound fraction of imatinib and N-desmethyl imatinib in human plasma.

Therapeutic drug monitoring (TDM) of imatinib (IM) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. There was a significant correlation between unbound concentration and clinical response and toxicity, compared with total plasma concentrations, and the quantification of unbound IM and its metabolite, N-desmethyl imatinib (NDI) are of interest for TDM. However, traditional unbound drug separation methods have shortcomings, especially are susceptible to non-specific binding (NSB) of drugs to the polymer-constructed components of filter membranes, which are difficult to avoid at present. Hence it is necessary to developed a reliable separation method for the analysis of the unbound fraction of IM and NDI in TDM. We developed and validated an hollow fiber solid phase microextraction (HF-SPME) method coupled with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) that to measure unbound IM and NDI concentration in human plasma. It used the NSB phenomenon and solve the NSB problem. The preparation procedure only involves a common vortex and ultrasonication without dilution of samples and modification of membrane. A total of 50 chronic myeloid leukemia (CML) patients were enrolled in our study. The relationship between the unbound and total concentrations for IM and NDI, as well as the concentration ratios of NDI to IM in 50 clinical plasma samples were investigated. The extraction recovery is high to 95.5-106 % with validation parameters for the methodological results were all excellent. There were both a poor linear relationship between the unbound and total concentrations for IM (r2=0.504) and NDI (r2=0.201) in 50 clinical plasma samples. The unbound concentration ratios of NDI to IM varied widely in CML patients. The determination of unbound IM and NDI concentration is meaningful and necessary. The developed HF-SPME method is simple, accurate and precise that could be used to measure unbound IM and NDI concentration in clinical TDM.

Cerebral Ischemic Coma Model Induced by Modified Four-Vessel Occlusion.

Coma caused by cerebral ischemia is the most serious complication of cerebral ischemia. Four-vessel occlusion can establish a cerebral ischemic coma model for disease research and drug development. However, the commonly used four-vessel occlusion method mainly involves inserting an electrocoagulation pen into the bilateral pterygoid foramen of the first cervical vertebra behind the neck to electrocoagulate the vertebral arteries. This process carries the risk of incomplete electrocoagulation, bleeding, and damage to the brainstem and spinal cord. Twenty-four hours after surgery, re-anesthetized rats undergo carotid artery ligation in front of the neck. Two surgeries expose the rats to a higher risk of infection and increase the experimental period. In this study, during a single surgical procedure, an anterior cervical incision was used to locate the key site where the vertebral artery penetrates the first cervical vertebra. The bilateral vertebral arteries were electrocauterized under visual conditions, while the bilateral common carotid arteries were separated to place loose knots. When the rats showed consciousness of the inversion reaction, the bilateral common carotid arteries were quickly ligated to induce ischemic coma. This method can avoid the risk of infection caused by two surgical operations and is easy to perform with a high success rate, providing a useful reference for relevant practitioners.

Efficacy and safety of BaitouWeng decoction for ulcerative colitis: A meta-analysis of randomized and controlled trials.

BACKGROUND: To systematically evaluate the therapeutic effect of BaitouWeng Decoction in patients with ulcerative colitis (UC), evaluate its safety and effectiveness, and provide a reference for clinical medication. METHODS: The research literature on the treatment of UC with BaitouWeng Decoction was searched in databases such as China National Knowledge Infrastructure, Wanfang Data, VIP database for Chinese Technical Periodicals, Chinese BioMedical Literature Database, and PubMed. The literature was screened by setting inclusion and exclusion criteria, strictly following the inclusion and exclusion criteria, and following the search strategy for literature screening, data extraction, and methodological quality evaluation. According to the Cochrane System Evaluation Manual, methodological quality evaluation was conducted on the included studies using the bias risk assessment tool for randomized controlled trials. For meta-analysis, Review Manager software was used. RESULTS: A total of 24 articles were included, including 2131 patients. Meta-analysis showed that compared with conventional Western medicine, BaitouWeng Decoction can significantly improve the effective rate (odds ratio = 5.10, 95% confidence interval [CI] [3.74-6.96], P < .00001), reduce the traditional Chinese medicine syndrome score (mean difference [MD] = -4.23, 95% CI [-5.17--3.30], P < .00001), Baron endoscopic score (MD = -0.68, 95% CI [-0.78--0.58], P < .00001), and intestinal lesion activity score (MD = -2.29, 95% CI [-1.15--1.03], P < .00001); improve serum factors and reduce serum tumor necrosis factor α levels (MD = -16.84, 95% CI [-19.92--13.76], P < .00001), serum interleukin-8 levels (MD = -10.41, 95% CI [-10.87--9.95], P < .00001), and increased serum interleukin-10 levels (MD = 4.96, 95% CI [2.76-7.16], P < .00001). CONCLUSION: BaitouWeng Decoction has good efficacy and safety in treating UC. BaitouWeng Decoction improved the symptoms of colitis injury and inhibited inflammatory response. However, more rigorously designed randomized controlled trials with blinding, concealment, and placebo controls should be conducted on Baitouweng decoction to generate higher quality evidence and longer-term studies on sustained benefits are needed.

Injective hydrogel loaded with liposomes-encapsulated MY-1 promotes wound healing and increases tensile strength by accelerating fibroblast migration via the PI3K/AKT-Rac1 signaling pathway.

Failed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1-34), we previously designed a novel PTH analog, PTH(3-34)(29-34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA-MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.

Widespread phthalate esters and monoesters in the aquatic environment: Distribution, bioconcentration, and ecological risks.

Field research on phthalate monoesters (MPEs) and their relationships with phthalate esters (PAEs) is limited, especially in wild fishes. Here, PAEs and MPEs were measured in surface water, sediment, and wild fish collected from a representative river basin with high economic development. Several metabolites of emerging plasticizers, such as mono(3,5,5-trimethyl-1-hexyl) phthalate and mono(6-oxo-2-propylheptyl) phthalate, have already existed in fish with high detection frequencies (95 % and 100 %). Monobutyl phthalate and mono(2-ethylhexyl) phthalate were the predominant MPEs in fish and natural environment (surface water and sediment), while bis(2-ethylhexyl) phthalate was the most abundant PAEs in all matrices. The total concentrations (median) of 9 PAEs and 16 MPEs were 5980 and 266 ng/L in water, 231 and 10.6 ng/g (dw) in sediment, and 209 and 32.5 ng/g (ww) in fish, respectively. The occurrence of MPEs was highly related to their parent PAEs, with similar spatial distribution characteristics in the aquatic environments. Moreover, municipal wastewater discharge was recognized as the main source of MPEs in the research area. Fish species can accumulate targeted chemicals, and it seems more MPEs were from the PAE degradation in fish other than the direct uptake of MPEs in water. Parent PAEs showed higher ecological risk than their corresponding metabolites.

A Modified Model Preparation for Middle Cerebral Artery Occlusion Reperfusion.

The middle cerebral artery occlusion reperfusion (MCAO/R) model is crucial for understanding the pathological mechanisms of stroke and for drug development.However, among the commonly used modeling methods, the Koizumi method often faces scrutiny due to its ligation of the common carotid artery (CCA) and its inability to achieve adequate reperfusion. Similarly, the Longa method has been criticized for disconnecting and ligating the external carotid artery (ECA). This study aims to introduce a modified model preparation method that preserves the integrity of the ECA, involves inserting a monofilament nylon suture through the CCA, repairing the ligated CCA incision, and maintaining reperfusion from the CCA. Reperfusion of blood flow was confirmed using laser speckle flow imaging. Evaluation methods such as the Longa scale, Modified Neurological Severity Score, triphenyltetrazolium chloride (TTC) staining, and immunofluorescence labeling of neurons demonstrated that this approach could induce stable ischemic nerve damage. This modified MCAO/R model protocol is simple and stable, providing valuable guidance for practitioners in the field of cerebral ischemia.

Disembedding and re-embedding: the online interaction mechanisms of divorced youth in China.

Introduction: In recent years, China's divorce rates have remained high, especially in metropolitan areas such as Beijing and Shanghai, where rates reach up to 40%. Additionally, there has been a notable shift towards younger demographics in divorce cases. In a society that highly values marital harmony, divorce is often seen as a cultural transgression. Anthony Giddens' theory of disembedding and re-embedding provides a useful framework for understanding these changes. This study addresses a gap in literature by focusing on the online social interactions of divorced Chinese youth, exploring their use of dating apps for emotional support and social reconnections. Methods: This qualitative study employed semi-structured interviews with 19 divorced young adults in China who engaged with dating apps such as Momo, Tantan, and Soul. Participants were recruited via Douban and Xiaohongshu. The interviews, conducted through WeChat voice calls and Tencent Meetings, lasted 45-70 minutes each. Data was analyzed using Nvivo12 to understand the disembedding and re-embedding processes in their online interactions, exploring themes such as motivations, self-presentation, and the transition from online to offline engagements. Results and discussion: The findings reveal that these individuals face societal challenges, biases, and the residual effects of past marriages, leading them to seek refuge in online environments to avoid stigmatization. In digital spaces, they cautiously engage, revealing a lack of confidence through selective self-disclosure. Their goals range from forming same-sex and opposite-sex friendships to seeking new romantic relationships, indicating a nuanced approach to remarriage and challenging stereotypes of dating app users. Re-engaging online, they discover social support and a sense of community, which aids in regaining confidence post-divorce, underscoring the complex interplay between societal influences and individual adaptation strategies in the digital age. The study highlights the unique challenges faced by this demographic, including maintaining anonymity and dealing with societal prejudices. Future research should consider a broader age range and gender differences to provide a more comprehensive understanding of the online behaviors and experiences of divorced individuals.

Extraction of Heracleum dissectum soluble dietary fiber by different methods: Structure and antioxidant properties.

Heracleum dissectum is rich in nutrients, but there is little research on its soluble dietary fiber (SDF). In this study, SDF from H. dissectum was extracted by enzyme extraction (E-SDF), enzyme chemical extraction (EC-SDF), and fermentation extraction (F-SDF). The composition, molecular weight (Mw), structural characterization, and antioxidant activity of SDF extracted by the three methods were compared. This study showed that different extraction methods lead to differences in their structure. The Mw results showed that F-SDF had the largest Mw, the structure of SDF could be destroyed by enzymatic hydrolysis, and large molecules could be converted into small molecules. The monosaccharide composition analysis showed that the main sugars of E-SDF, EC-SDF, and F-SDF were galacturonic acid and galactose, and the main components of the three SDF samples were hemicellulose hydrolyzed pectin and soluble polysaccharide. Notably, E-SDF had the greatest antioxidant effect at the same concentration. In summary, different extraction methods can affect the structure and antioxidant capacity of H. dissectum SDF, among which E-SDF has potential as a functional food ingredient.

Auditory change detection and visual selective attention: association between MMN and N2pc.

While the auditory and visual systems each provide distinct information to our brain, they also work together to process and prioritize input to address ever-changing conditions. Previous studies highlighted the trade-off between auditory change detection and visual selective attention; however, the relationship between them is still unclear. Here, we recorded electroencephalography signals from 106 healthy adults in three experiments. Our findings revealed a positive correlation at the population level between the amplitudes of event-related potential indices associated with auditory change detection (mismatch negativity) and visual selective attention (posterior contralateral N2) when elicited in separate tasks. This correlation persisted even when participants performed a visual task while disregarding simultaneous auditory stimuli. Interestingly, as visual attention demand increased, participants whose posterior contralateral N2 amplitude increased the most exhibited the largest reduction in mismatch negativity, suggesting a within-subject trade-off between the two processes. Taken together, our results suggest an intimate relationship and potential shared mechanism between auditory change detection and visual selective attention. We liken this to a total capacity limit that varies between individuals, which could drive correlated individual differences in auditory change detection and visual selective attention, and also within-subject competition between the two, with task-based modulation of visual attention causing within-participant decrease in auditory change detection sensitivity.

Triphenylphosphine-bonded coumaranone dyes realize dual color imaging of mitochondria and nucleoli.

Probing intracellular organelles with fluorescent dyes offers opportunities to understand the structures and functions of these cellular compartments, which is attracting increasing interests. Normally, the design principle varies for different organelle targets as they possess distinct structural and functional profiles against each other. Therefore, developing a probe with dual intracellular targets is of great challenge. In this work, a new sort of donor-π-bridge-acceptor (D-π-A) type coumaranone dyes (CMO-1/2/3/4) have been prepared. Four fluorescent probes (TPP@CMO-1/2/3/4) were then synthesized by linking these coumaranone dyes with an amphiphilic cation triphenylphosphonium (TPP). Interestingly, both TPP@CMO-1 and TPP@CMO-2 exhibited dual color emission upon targeting to two different organelles, respectively. The green emission is well localized in mitochondria, while, the red emission realizes nucleoli imaging. RNA is the target of TPP@CMOs, which was confirmed by spectroscopic analysis and computational calculation. More importantly, the number and morphology changes of nucleoli under drug stress have been successfully evaluated using TPP@CMO-1.

Impact of homocysteine on acute ischemic stroke severity: possible role of aminothiols redox status.

BACKGROUND: Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients. METHODS: A total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score. RESULTS: The reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05. CONCLUSIONS: The reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.

Risk factors for poor outcomes in patients with acute lower leg compartment syndrome: a retrospective study of 103 cases.

PURPOSE: The primary aim of this study was to investigate the risk factors associated with poor outcomes following acute compartment syndrome (ACS) of lower leg. The secondary objective was to determine if delayed fasciotomy is linked to poor outcomes. METHODS: In this retrospective case control study approved by the institutional review board, we identified 103 patients with ACS of the lower leg. Poor outcome was defined as a composite variable that included limb amputation, neurological deficit and contracture. Among these, 44 patients exhibited poor outcome while 59 patients demonstrated a good outcome. Patient-related factors, laboratory values, and treatment-related factors were analyzed using electronic medical records. Univariate statistical and logistic regression analyses were conducted to determine significance. RESULTS: Bivariate analyses showed that the mechanism of injury (P = 0.021), open injury (P = 0.001), arterial injury (P<0.001), hemoglobin levels (HB) (P < 0.001), white blood cell count (WBC) (P = 0.008), albumin levels (ALB) (P<0.001), creatine kinase levels (CK) at presentation (P = 0.015), CK at peak (P<0.001), creatine kinase levels (Ca) (P = 0.004), dehydrating agent (P = 0.036), and debridement (P = 0.005) were found to be associated with the risk of poor outcomes. Logistic regression analyses revealed that arterial injury [ P< 0.001, OR = 66.172, 95% CI (10.536, 415.611)] was an independent risk factor for poor outcomes. However, HB [P = 0.005, OR = 0.934, 95% CI (0.891, 0.979)] was a protective factor against poor outcomes. Receiver operating characteristic (ROC) curve analysis showed that the cut-off values of HB to prevent poor outcome following ACS was 102.45 g/L. CONCLUSIONS: ACS of the lower leg is a serious complication often associated with a poor prognosis. Patients with arterial injury or lower HB have a significantly increased risk of having poor outcomes. Poor outcomes were not found to be associated with the timing of fasciotomy in this study.

Overexpression of YTHDF3 increases the specific productivity of the recombinant protein in CHO cells by promoting the translation process.

Due to their high-quality characteristics, Chinese hamster ovary (CHO) cells have become the most widely used and reliable host cells for the production of recombinant therapeutic proteins in the biomedical field. Previous studies have shown that the m6A reader YTHDF3, which contains the YTH domain, can affect a variety of biological processes by regulating the translation and stability of target mRNAs. This study investigates the effect of YTHDF3 on transgenic CHO cells. The results indicate that stable overexpression of YTHDF3 significantly enhances recombinant protein expression without affecting host cell growth. Transcriptome sequencing indicated that several genes, including translation initiation factor, translation extension factor, and ribosome assembly factor, were upregulated in CHO cells overexpressing YTHDF3. In addition, cycloheximide experiments confirmed that YTHDF3 enhanced transgene expression by promoting translation in CHO cells. In conclusion, the findings in this study provide a novel approach for mammalian cell engineering to increase protein productivity by regulating m6A.

Distribution and analysis of subacromial spurs and the relationship with acromial classification and angle in healthy individuals.

BACKGROUND: Subacromial spurs are considered the one of the pathology underlying shoulder impingement syndrome. Furthermore, few studies have focused on the morphology of the subacromial spurs in normal Chinese people. This study aimed to study the spur distribution and to illustrate the morphology of spurs, which may help guide the extent of acromioplasty. METHODS: A total of 93 normal individuals were enrolled, and both shoulders of all enrolled individuals were analyzed. The subjects were divided and classified into three different groups by ages: group I = 18-40 years, group II = 41-60 years, and group III ≥ 61 years. The osteophyte distribution, osteophyte area, subacromial surface area and osteophyte area/subacromial surface area ratio were measured and illustrated using Mimics and 3-matic software. The shape of the acromion was classified according to the Bigliani and Morrison classification system. The acromial angle was also classified. Then, the relationship between osteophytes, acromial classification and acromial angle was analyzed. RESULTS: Type II (curved shape) was the most common type of acromion, and the hooked shape was a rare form. A significant increase in the left subacromial surface area in males was observed in group III compared with group I (P < 0.001) and group II (P = 0.004). The total spur/subacromial area ratio was significantly higher in group II than I. An obvious increase in the right subacromial area was observed in group III compared with group I (P = 0.004). Furthermore, there was a significant increase in the right spur area (P = 0.021) and total spur/subacromial area ratio (P = 0.006) in females in group II compared with group I. Fewer spurs were observed on the left than on the right side (p = 0.0482). One spur was most common among type II acromions (29/36) (80.56%) on the left side and the right side (34/52, 65.38%). CONCLUSIONS: Spurs osteophytes are mainly distributed with an irregular shape and mostly run through the medial and lateral sides of the subacromial surface in normal subjects. The characteristics of subacromial spurs are so diverse that a surgeon must conduct subacromial decompression completely based on the morphology of individual spurs.

Discovery of Melittin as Triple-Action Agent: Broad-Spectrum Antibacterial, Anti-Biofilm, and Potential Anti-Quorum Sensing Activities.

The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics.

Integrating Transcriptome and Chemical Analyses to Provide Insights into Biosynthesis of Terpenoids and Flavonoids in the Medicinal Industrial Crop Andrographis paniculate and Its Antiviral Medicinal Parts.

Andrographis paniculata is a medicinal plant traditionally used to produce diterpene lactones and flavonoids, which possess various biological activities. Widely distributed in China, India, and other Southeast Asia countries, A. paniculata has become an important economic crop, significantly treating SARS-CoV-2, and is being cultivated on a large scale in southern China. The biosynthesis of active ingredients in A. paniculata are regulated and controlled by genes, but their specific roles are still not fully understood. To further explore the growth regulation factors and utilization of its medicinal parts of this industrial crop, chemical and transcriptome analyses were conducted on the roots, stems, and leaves of A. paniculata to identify the biosynthesis pathways and related candidate genes of the active ingredients. The chemical analysis revealed that the main components of A. paniculata were diterpene lactones and flavonoids, which displayed potential ability to treat SARS-CoV-2 through molecular docking. Moreover, the transcriptome sequencing annotated a total of 40,850 unigenes, including 7962 differentially expressed genes. Among these, 120 genes were involved in diterpene lactone biosynthesis and 60 genes were involved in flavonoid biosynthesis. The expression of diterpene lactone-related genes was the highest in leaves and the lowest in roots, consistent with our content determination results. It is speculated that these highly expressed genes in leaves may be involved in the biosynthesis pathway of diterpenes. Furthermore, two class Ⅰ terpene synthases in A. paniculata transcriptome were also annotated, providing reference for the downstream pathway of the diterpene lactone biosynthesis. With their excellent market value, our experiments will promote the study of the biosynthetic genes for active ingredients in A. paniculata and provide insights for subsequent in vitro biosynthesis.

Comparison of triplanar chevron osteotomy with chevron osteotomy in hallux valgus treatment for the prevention of transfer metatarsalgia.

Hallux valgus (HV) is often accompanied by metatarsalgia. This study compared the radiological and clinical outcomes of new triplanar chevron osteotomy (TCO) and chevron osteotomy (CO) in the treatment of HV, especially for patients with plantar callosities and metatarsalgia. In this retrospective analysis, 90 patients (45 patients per group) with mild to moderate HV and plantar callosities were treated with TCO and CO from July 2020 to January 2022. In both procedures, the apex was located in the center of the head of the first metatarsal bone, and the CO was oriented towards the fourth MTPJ at a 60° angle. Plantar-oblique chevron osteotomy was defined as chevron osteotomy and a 20° plantar tilt; TCO was defined as plantar-oblique chevron osteotomy-based metatarsal osteotomy with a 10° tilt towards the metatarsal head. Primary outcome measures included preoperative and postoperative hallux valgus angle, 1 to 2 intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), first metatarsal length (FML), and second metatarsal head height X-ray images; clinical measurements, including visual analogue scale and American Orthopaedic Foot & Ankle Society (AOFAS) scores; changes in callosity grade and area; and changes in the number of people with metatarsalgia. Secondary outcomes included complications, recurrence rates, and cosmetic appearance. The hallux valgus angle, IMA, and DMAA were significantly lower after surgery (P  < .001) in all patients. In the TCO group, the mean FML and second metatarsal head height increased significantly postoperatively (P < .001). The AOFAS and visual analogue scale scores improved postoperatively in both groups (P < .001). All patients experienced satisfactory pain relief and acceptable cosmesis. The plantar callosity areas were smaller postoperatively in both the TCO and CO groups, but the change in the area (Δarea) in the TCO group significantly differed from that in the CO group (P < .001). The number of postoperative patients with metatarsalgia and the plantar callosity grade were both significantly lower in the TCO group than in the CO group after osteotomy (P < .05). TCO prevents dorsal shift of the metatarsal head and preserves and even increases FML, thereby preventing future metatarsalgia in patients. Therefore, compared with CO, TCO has better orthopedic outcomes and is an effective method for treating mild to moderate HV and preventing transfer metatarsalgia.

Overactivated contextual visual perception and response to a single dose of methylphenidate in children with ADHD.

The pathogenesis of overactivated visual perception in attention-deficit hyperactivity disorder (ADHD) remains unclear, which is interpreted as a cognitive compensation. The existing studies have proposed that perceptual abnormalities in neurodevelopmental disorders are associated with dysfunction of the contextual knowledge system, which influences the development and formation of perception. We hypothesized that alterations in contextual states may also be responsible for inducing perceptual abnormalities in ADHD. Therefore, the present study evaluated the characteristics of pre-stimulus alpha and its response to a single dose of methylphenidate (MPH). A total of 135 Chinese children participated in the first study, including 70 children with ADHD (age = 10.61 ± 1.93 years, female = 17) and 65 age- and sex-matched control children (age = 10.73 ± 1.93 years, female = 20). The second clinical trial included 19 Chinese children with ADHD (age = 11.85 ± 1.72 years, female = 4), with an identical visual spatial search task. Pre-stimulus alpha oscillations and P1 activity were significantly greater in children with ADHD than in the controls. Overactivated pre-stimulus alpha positively predicted P1. Both pre-stimulus alpha and P1 overactivation have beneficial effects on cognitive performance in children with ADHD. No intervening effect of a single dose of MPH on the compensatory activation of pre-stimulus alpha and P1 were observed. Our findings extended the perceptual activation to the contextual knowledge system, suggesting that compensatory perception in children with ADHD is more likely to be a top-down regulated cognitive operational process.