Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model.

JOURNAL/nrgr/04.03/01300535-202503000-00030/figure1/v/2024-06-17T092413Z/r/image-tiff Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

HECTD2 as a target for veratric acid in the regulation of ferroptosis in renal cell carcinoma.

Function of HECTD2 in renal cell carcinoma malignant progression is undefined. Molecular mechanism behind anti-cancer effects of veratric acid (VA) from traditional Chinese medicine (TCM) is underexplored. The Cancer Genome Atlas was leveraged to study HECTD2 expression in renal cell carcinoma and its relationship with histological grading. Kaplan-Meier survival analysis was performed. HECTD2 expression was detected in cancer cells and tissues via qRT-PCR and immunohistochemistry. GPX4 and SLC7A11 expression in tumor samples with high or low HECTD2 expression was examined by immunohistochemistry, cell viability by CCK8, cell proliferation by colony formation assay, lipid ROS and mitochondrial superoxide levels by flow cytometry, Fe2+ and MDA content by assay kits, and GPX4 and SLC7A11 proteins by western blot. SeeSAR software screened TCM small molecule compounds with highest affinity to HECTD2, confirmed with cellular thermal shift assay. VA IC50 was measured by CCK8. Xenograft model was developed and treated with VA. Tumor size and weight were monitored, with immunohistochemistry to detect HECTD2 expression in tumors and assess ferroptosis-related markers. HECTD2 was overexpressed in tumor tissues and cells, which positively correlated with histological grading. HECTD2 depletion inhibited cell vitality and proliferation, raised intracellular lipid ROS, mitochondrial superoxide, Fe2+, and MDA. HECTD2 was a target with highest VA affinity. In vitro and vivo experiments concurred that VA treatment hindered malignancy of renal cell carcinoma and enhanced its susceptibility to ferroptosis. HECTD2 supports ferroptosis resistance in renal cell carcinoma, but VA, through its targeting of HECTD2, initiates ferroptosis, showcasing its anti-cancer efficacy.

Dress Code Monitoring Method in Industrial Scene Based on Improved YOLOv8n and DeepSORT.

Deep learning-based object detection has become a powerful tool in dress code monitoring. However, even state-of-the-art detection models inevitably suffer from false alarms or missed detections, especially when handling small targets such as hats and masks. To overcome these limitations, this paper proposes a novel method for dress code monitoring using an improved YOLOv8n model, the DeepSORT tracking, and a new dress code judgment criterion. We improve the YOLOv8n model through three means: (1) a new neck structure named FPN-PAN-FPN (FPF) is introduced to enhance the model's feature fusion capability, (2) Receptive-Field Attention convolutional operation (RFAConv) is utilized to better capture the difference in information brought by different positions, and a (3) Focused Linear Attention (FLatten) mechanism is added to expand the model's receptive field. This improved YOLOv8n model increases mAP while reducing model size. Next, DeepSORT is integrated to obtain instance information across multi-frames. Finally, we adopt a new judgment criterion to conduct real-scene dress code monitoring. The experimental results show that our method effectively identifies instances of dress violations, reduces false alarms, and improves accuracy.

Effects of aerobic exercise on executive function of healthy middle-aged and older adults: A systematic review and meta-analysis.

BACKGROUND: The deterioration of executive function is a hallmark of cognitive aging. Reports indicate that signs of decline in executive function begin to emerge as early as middle age. Aerobic exercise improves executive function in healthy middle-aged and older adults, but the optimal exercise prescription variables are still unclear. OBJECTIVE: To investigate the effects of aerobic exercise on executive function of healthy middle-aged and older adults and explore the dose-response relationship and moderators. METHODS: We conducted comprehensive searches of PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, PsycINFO, and SPORTDiscus for English literature, and CNKI, WanFang, and VIP for Chinese literature, covering the period from inception until April 25, 2024. Randomized controlled trials examining the effect of aerobic exercise on executive function in healthy middle-aged and older adults aged 45 or older were included. The Cochrane Collaboration's RoB2 tool was used to assess the methodological quality of the included studies. And subgroup analyses and meta-regressions were conducted to elucidate the impact of aerobic exercise on executive function. RESULTS: Forty-two eligible randomized controlled trials, involving a total of 2881 participants, met the inclusion criteria for the systematic review and meta-analysis. The pooled results showed that aerobic exercise had positive effects on improving cognitive flexibility (Hedge's g = 0.343, p < 0.001), working memory (Hedge's g = 0.392, p < 0.001), and inhibitory control (Hedge's g = 0.229, p < 0.001) in healthy middle-aged and older adults. However, it did not demonstrate an improvement in planning (Hedge's g = 0.094, p = 0.440). The dose-response relationships between different exercise parameters and subdomains of executive functions revealed that the largest effects on cognitive flexibility were observed after 13-24 weeks of progression-intensity mind-body exercise, 46-60 min per session, and 5-7 days per week. Regarding working memory, the largest effects were observed after 13-24 weeks of progression-intensity general aerobic exercise, 20-45 min per session, and 5-7 days per week. For inhibitory control, the greatest effects were noted after 13-24 weeks of low-intensity general aerobic exercise, 20-45 min per session, and 3-4 days per week. CONCLUSION: Aerobic exercise can significantly improve cognitive flexibility, working memory, and inhibitory control in healthy middle-aged and older adults. The effect of aerobic exercise on different aspects of executive function is influenced by specific exercise parameters, suggesting that personalized aerobic exercise programs may be more effective for enhancing executive function of healthy middle-aged and older adults.

Antibacterial and cytotoxic metabolites produced by Streptomyces tanashiensis BYF-112 isolated from Odontotermes formosanus.

Chemical investigations of the termite-associated Streptomyces tanashiensis BYF-112 resulted in the discovery of four novel alkaloid derivatives: vegfrecines A and B (1 and 2), exfoliazone A (3), and venezueline H (7), in addition to nine known metabolites (4-6, 8-13). The structures of these compounds were elucidated through comprehensive spectroscopic analysis and comparison with existing literature data. Antibacterial assays revealed that viridomycin A (11) exhibited potent antibacterial activity against Staphylococcus aureus, with a zone of inhibition (ZOI) of 12.67 mm, in comparison to a ZOI of 17.67 mm for the positive control gentamicin sulfate. Viridomycin A (11) showed moderate activity against Micrococcus tetragenus and Pseudomonas syringae pv. actinidae, with ZOI values of 15.50 and 14.33 mm, respectively, which were inferior to those of gentamicin sulfate (34.67 and 24.00 mm). Viridomycin F (12) also exhibited moderate antibacterial effects against S. aureus, M. tetragenus, and P. syringae pv. actinidae, with ZOI values of 8.33, 16.50, and 10.83 mm, respectively. Cytotoxicity assays demonstrated that viridobruunine A (5), exfoliazone (6), viridomycin A (11), and X-14881E (13) exhibited significant cytotoxicity against human malignant melanoma (A375), ovarian cancer (SKOV-3), and gastric cancer (MGC-803) cell lines, with IC50 values ranging from 4.61 to 19.28 µmol·L-1. Furthermore, bioinformatic analysis of the complete genome of S. tanashiensis suggested a putative biosynthetic gene cluster (BGC) responsible for the production of compounds 1-12. These findings indicate that the secondary metabolites of insect-associated S. tanashiensis BYF-112 hold promise as potential sources of novel antibacterial and anticancer agents.

Survey of Medical Access for Inpatients in Center for Cleft Lip and Palate Treatment: Social Media Usage Preferences and Influencing Factors in China.

This study investigated the role of social media in the process of cleft lip and palate patients selecting surgeons. Patients utilized social media to obtain information about their health care providers and treatment teams and relied on this information to guide their decisions on where to seek medical care. A retrospective survey was conducted among patients who underwent surgery in our department from December 2020 to May 2023. Through an anonymous questionnaire titled "Factors Influencing the Decision to Choose a Particular Cleft Surgeon," we explored how patients discovered their primary surgeon via social media and the factors they deemed most important in selecting their surgeon. The questionnaire was completed by patients or their guardians. The cleft lip and palate patient population exhibited a distinct geographical distribution. A total of 548 individuals participated in the survey on media usage. Search engines (Baidu) were the most frequently visited (30.5%), followed by short video platforms (TikTok and Kwai), accounting for 21.7%, the hospital's official website at 20.8%, and WeChat at 15%. The primary factors influencing the selection of surgeons were the surgeon's reputation (66.2%), the hospital/medical team's reputation (49.2%), the quality of communication during consultations (15.4%), and the surgical outcomes depicted in postoperative photos (6.9%). The Internet remains the primary source of health information. Therefore, it is crucial to not only provide accurate medical information but also effectively communicate complex medical knowledge through easily accessible media channels in a manner that is comprehensible to patients.

Baicalein inhibits cerebral ischemia-reperfusion injury through SIRT6-mediated FOXA2 deacetylation to promote SLC7A11 expression.

Ischemic stroke (IS) poses a serious threat to patient survival. The inhibition of ferroptosis can effectively alleviate ischemia-reperfusion (I/R) injury, suggesting potential targets in the ferroptosis pathway for the treatment of ischemic stroke. In this study, MCAO/R mice and OGD/R-induced HT22 cell were constructed. It was found that Baicalein decreased ROS, MDA, and Fe2+ levels, upregulated GSH levels, and enhanced the expression of ferroptosis-related proteins (GPX4 and SLC7A11), downregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3), and upregulated the expression of an anti-apoptotic protein (Bcl-2), ameliorating cerebral I/R injury. In animal and cell models, SIRT6 is downregulated, and FOXA2 expression and acetylation levels are abnormally upregulated. SIRT6 inhibited FOXA2 expression and acetylation. Baicalein promoted FOXA2 deacetylation by upregulating SIRT6 expression. FOXA2 transcriptionally inhibits SLC7A11 expression. In Conclusion, Baicalein inhibited apoptosis and partially suppressed the role of ferroptosis to alleviate cerebral I/R injury via SIRT6-mediated FOXA2 deacetylation to promote SLC7A11 expression.Significance Statement Ischemic stroke (IS) is a disease of the central nervous system with high mortality and morbidity rates. Currently, effective treatments for IS are limited. Therefore, it is urgent to develop novel treatment methods. Ferroptosis inhibitors and iron chelating agents can effectively alleviate IS neuronal damage, suggesting potential targets in the ferroptosis pathway for the IS treatment. This study confirmed, for the first time, that baicalein promoted FOXA2 deacetylation by upregulating SIRT6 expression, thereby inhibiting FOXA2 transcription, leading to the upregulation of SLC7A11 expression, inhibition of apoptosis, and partial suppression of the role of ferroptosis, thus inhibiting cell apoptosis and ultimately alleviating I/R injury in IS. Our study suggests that SIRT6/FOXA2 is a target of baicalein in IS therapy.

Altered brain activity associated with premature ejaculation improved by electroacupuncture in rats.

Background: Premature ejaculation (PE) is linked with abnormal brain activity that is modifiable by electroacupuncture (EA). Aim: In this study we aimed to explore the central pathological mechanism underlying EA in treating PE. Methods: Six-week-old male Sprague-Dawley rats were divided into a PE group (n = 8) and a control group (n = 8) according to ejaculatory frequency during copulatory behavior. All rats underwent EA at the Zusanli acupoint (ST-36) for 4 weeks. Magnetic resonance imaging data were collected before and after EA. Outcomes: The behavioral parameters, plasma norepinephrine levels, fractional amplitude of low frequency fluctuation (fALFF), and regional homogeneity (ReHo) were evaluated. Results: The PE group ejaculated more times with shorter latency compared with controls. After EA, the ejaculation frequency of the PE group decreased, and the ejaculation latency period increased, with no changes observed in the control group. Norepinephrine levels were higher in the PE group than in the controls and were positively correlated with ejaculation frequency and negatively correlated with ejaculation latency. The PE group showed lower fALFF in the right striatum and higher ReHo in the brainstem compared with controls. After EA, controls showed decreased fALFF in the right striatum, left olfactory bulb, and dorsal fornix and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, prelimbic system, right basal forebrain region, septal region, and olfactory bulb, while the model group exhibited increased fALFF in the right hypothalamic region, decreased fALFF in the left globus pallidum and right basal forebrain region and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, olfactory bulb, basal forebrain region, dentate gyrus, right dysgranular insular cortex, and striatum. Compared with the controls after EA, the model group showed increased ReHo of the right hypothalamic region and decreased ReHo of the right dysgranular insular cortex. Clinical Implications: These findings might enhance the understanding of PE and contribute to new, targeted therapies for PE. Strengths and Limitations: The therapeutic effects might be achieved by EA inhibiting the activity in brain regions involved in ejaculatory behavior. However, the curative effect of acupuncture might be underestimated due to some curative effects of sham acupuncture used in the control group. Conclusion: In conclusion, the ejaculatory frequency of rats may be reduced and ejaculation latency could be extended by EA at ST-36, which might be achieved by the effects of this treatment on brain activity.

A two-stage defect detection method for unevenly illuminated self-adhesive printed materials.

The process of printing defect detection usually suffers from challenges such as inaccurate defect extraction and localization, caused by uneven illumination and complex textures. Moreover, image difference-based defect detection methods often result in numerous small-scale pseudo defects. To address these challenges, this paper proposes a comprehensive defect detection approach that integrates brightness correction and a two-stage defect detection strategy for self-adhesive printed materials. Concretely, a joint bilateral filter coupled with brightness correction corrects uneven brightness properly, meanwhile smoothing the grid-like texture in complex printed material images. Then, in the first detection stage, an image difference method based on a bright-dark difference template group is designed to effectively locate printing defects despite slight brightness fluctuations. Afterward, a discriminative method based on feature similarity is employed to filter out small-scale pseudo-defects in the second detection stage. The experimental results show that the improved difference method achieves an average precision of 99.1% in defect localization on five different printing pattern samples. Furthermore, the second stage reduces the false detection rate to under 0.5% while maintaining the low missed rate.

Metal-Free Wet Chemistry for the Fast Gram-Scale Synthesis of γ-Graphyne and its Derivatives.

γ-Graphyne (GY), an emerging carbon allotrope, is envisioned to offer various alluring properties and broad applicability. While significant progress has been made in the synthesis of GY over recent decades, its widespread application hinges on developing efficient, scalable, and accessible synthetic methods for the production of GY and its derivatives. Here we report a facile metal-free nucleophilic crosslinking method using wet chemistry for fast gram-scale production of GY and its derivatives. This synthesis method involves the aromatic nucleophilic substitution reactions between fluoro-(hetero)arenes and alkynyl silanes in the presence of a catalytic amount of tetrabutylammonium fluoride, where the fluoride plays a crucial role in removing protective groups from alkynyl silanes and generating reactive alkynylides. Our comprehensive analysis of the as-prepared GY reveals a layered structure, characterized by the presence of the C(sp)-C(sp2) bond. The synthetic strategy shows remarkable tolerance to various functional groups and enables the preparation of diverse F-/N-rich GY derivatives, using electron-deficient fluoro-substituted (hetero)arenes as precursors. The feasibility of producing GY and derivatives from fluorinated (hetero)arenes through the metal-free, scalable, and cost-effective approach paves the way for broad applications of GY and may inspire the development of new carbon materials.

Genetic variation and phylogenetic analysis of 23 STR in Chinese Han population from Hainan, Southern China.

The forensic characteristics and genetic relationships of Hainan Han population are still not fully understood. The aim of this study was to investigate the forensic features and genetic variations of 23 short tandem repeat (STR) included in the HuaxiaTM Platinum system in Hainan Han and analyze the population genetic relationships between Hainan Han and other adjacent Chinese populations. The genetic polymorphisms of 23 STR loci included in the HuaxiaTM Platinum kit were evaluated from 2971 Hainan Han individuals. Comprehensive comparisons were conducted based on genetic distance, phylogenetic tree, multidimensional scaling and principal component analysis (PCA) to explore inter-population genetic relationship. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) of the 23 STR loci was 0.999 999 999 999 999 999 999 999 999 819 and 0.999 999 999 625 408, respectively. The investigated Hainan Han population has high genetic similarity with geographically close Han populations, while great genetic difference with other ethnic minorities, prominently in Yunnan Miao, Xinjiang Uygurs, Xinjiang Kazakh, and Tibetans. Our study found the 23 STR loci were highly polymorphic and suitable for forensic personal identification and paternity testing in Hainan Han population. Genetic similarity widely existed among Han populations from different regions, and significant genetic divergence existed between Han populations and some ethnic minorities. The populations genetic diversity and similarity were closely associated with ethnic origin and geographical distribution.

Performance investigation of a solar-driven cascaded phase change heat storage cross-seasonal heating system for plateau applications.

The mismatch between solar radiation resources and building heating demand on a seasonal scale makes cross-seasonal heat storage a crucial technology, especially for plateau areas. Utilizing phase change materials with high energy density and stable heat output effectively improves energy storage efficiency. This study integrates cascaded phase change with a cross-seasonal heat storage system aimed at achieving low-carbon heating. The simulation analyzes heat distribution and temperature changes from the heat storage system to the heating terminal. The results indicate that although the solar collectors operate for 26.3% of the total heat storage and heating period, the cumulative heat stored is 45.4% higher than the total heating load. Heat transferred by the cross-seasonal heat storage system accounts for up to 61.2% of the total heating load. Therefore, the system reduces fuel consumption by 77.6% compared to conventional fossil fuel heating systems. Moreover, radiant floor heating terminals, with a wide range of operating temperatures, match well with cascaded phase change heat storage and can reduce operation time by 19.5% and heat demand by 5.2% compared to conventional radiators. In addition to demonstrating the feasibility of applying cascaded phase change technology in cross-seasonal heat storage heating, this study reveals the lifecycle sustainability due to the shortened heat storage period. The configuration, parameters, and simulation results provide a reference basis for system application and design.

SELENBP1 Inhibits the Warburg Effect and Tumor Growth by Reducing the HIF1α Expression in Colorectal Cancer.

INTRODUCTION: Colorectal cancer (CRC) is experiencing a significant increase in both incidence and mortality rates globally. The expression of Selenium-binding protein 1 (SELENBP1) has been reported to be notably downregulated in various malignancies, yet its biological functions and cellular mechanisms in CRC remain incompletely understood. METHOD: In our investigation, we observed the downregulation of SELENBP1 in CRC tissues through quantitative real-time PCR and western blotting and identified a positive correlation between higher SELENBP1 expression and improved survival prognosis using Kaplan-Meier survival analysis. Through loss-of-function and gain-of-function studies, we demonstrated the tumor-suppressive roles of SELENBP1 in CRC, supported by results from both in vitro and in vivo experiments. Furthermore, we uncovered the pivotal functions of SELENBP1 in suppressing aerobic glycolysis in CRC cells by regulating glucose uptake, lactate generation, and extracellular acidification rate. RESULT: At a mechanistic level, we found that SELENBP1 inhibits the expression of the key glycolytic modulator hypoxia-inducible factor 1 subunit alpha (HIF1α), and the inhibition of glycolysis by SELENBP1 can be reversed by ectopic expression of HIF1α. Therefore, our study highlights the potential of SELENBP1 as a promising target for CRC therapy, given its significant impact on tumor suppression and reprogrammed glucose metabolism. CONCLUSION: These findings contribute to a deeper understanding of the molecular mechanisms underlying CRC progression and may pave the way for the development of targeted therapies for this challenging disease.

EMG-projected MEG high-resolution source imaging of human motor execution: Brain-muscle coupling above movement frequencies.

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trials needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing early-stage (-100 to 0 ms) M1 activity during ~l min recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and upper-gamma (60-90 Hz) bands in 13 healthy participants (26 datasets) and three presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) or gamma/upper-gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In three presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement-related brain-muscle coupling above the movement frequency and its harmonics.

A Concise and Accurate Method for Evaluating Alveolar Cleft ReconstructionDiet al Concise and Accurate Method for Evaluating.

Currently, there remain unresolved issues in the treatment of alveolar clefts, the resolution of which could greatly benefit many patients with cleft lip and palate. In alveolar cleft treatment research, a reliable tool for pre- and postoperative assessment is crucial. This study presents a concise and accurate method for postoperative evaluations of alveolar treatment, which can rapidly and accurately obtain the shape and volume of the newly formed bone. This study included helical computed tomography (CT) datasets of 20 patients who underwent alveolar bone grafting at our institute. Two observers independently measured the volume of newly formed bone in the patient's CT images one year postoperatively, with each observer performing the measurement twice. To acquire the volume of the newly formed bone at 1 year postoperatively, the model of the newly formed bone must be constructed first. The acquisition of this model involves Boolean operations on registered preoperative and postoperative cranial 3-dimensional (3D) images. The registration of the preoperative and postoperative models is performed in MIMICS software, and the registration results can be directly confirmed layer by layer on the CT images to ensure accuracy. The mean newly formed bone ratio in this study was 39.81%±17.96%, and the mean processing time was 05:11±01:41 minutes. The intraclass correlation coefficient for bone volume measurements between the two observers was 0.999, indicating high consistency and reproducibility. This method enhances accuracy, is time-efficient, and demonstrates high reliability in evaluating postoperative bone formation.

Development of amphipathic derivatives of thymol and carvacrol as potent broad-spectrum antibacterial agents.

In the current study, to discover novel antibacterial agents, we designed and synthesized 72 carvacrol and thymol derivatives by biomimicking the structure and function of cationic antimicrobial peptides (AMPs). Many of the derivatives showed good antibacterial activity, and compound thy2I exhibited the most potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.5 µg/mL to 8 µg/mL. Compound thy2I could kill both gram-positive and gram-negative bacteria via a membrane-targeting mechanism of action with a low frequency of resistance. In addition, thy2I had the advantages of good membrane selectivity, low toxicity in vitro and in vivo, and good plasma stability. The in vivo activity results revealed that thy2I exhibited a positive therapeutic effect in a mouse skin abscess model induced by Staphylococcus aureus ATCC29213. After thy2I treatment (10 mg/kg), the bacterial load of the S. aureus-infected abscesses was reduced by approximately 99.65 %. Our study suggests that thy2I may serve as an antibacterial lead for further clinical evaluation.

Chromosome-level assembly of Lindenbergia philippensis and comparative genomic analyses shed light on genome evolution in Lamiales.

Lamiales, comprising over 23,755 species across 24 families, stands as a highly diverse and prolific plant group, playing a significant role in the cultivation of horticultural, ornamental, and medicinal plant varieties. Whole-genome duplication (WGD) and its subsequent post-polyploid diploidization (PPD) process represent the most drastic type of karyotype evolution, injecting significant potential for promoting the diversity of this lineage. However, polyploidization histories, as well as genome and subgenome fractionation following WGD events in Lamiales species, are still not well investigated. In this study, we constructed a chromosome-level genome assembly of Lindenbergia philippensis (Orobanchaceae) and conducted comparative genomic analyses with 14 other Lamiales species. L. philippensis is positioned closest to the parasitic lineage within Orobanchaceae and has a conserved karyotype. Through a combination of Ks analysis and syntenic depth analysis, we reconstructed and validated polyploidization histories of Lamiales species. Our results indicated that Primulina huaijiensis underwent three rounds of diploidization events following the γ-WGT event, rather than two rounds as reported. Besides, we reconfirmed that most Lamiales species shared a common diploidization event (L-WGD). Subsequently, we constructed the Lamiales Ancestral Karyotype (LAK), comprising 11 proto-chromosomes, and elucidated its evolutionary trajectory, highlighting the highly flexible reshuffling of the Lamiales paleogenome. We identified biased fractionation of subgenomes following the L-WGD event across eight species, and highlighted the positive impacts of non-WGD genes on gene family expansion. This study provides novel genomic resources and insights into polyploidy and karyotype remodeling of Lamiales species, essential for advancing our understanding of species diversification and genome evolution.

Comparison of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma treated nonsurgically and proposal of a new stage grouping system.

OBJECTIVE: To compare the survival discrimination of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma (ASCC) treated nonsurgically and suggest a simple revised staging system with data from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Overall survival (OS) was the primary endpoint. Survival comparisons between the T and N stages and the different staging systems were performed using the Kaplan-Meier method and log-rank test, followed by correlation analysis and variable importance analysis (VIA). Additionally, multivariate analysis was employed to identify significant predictors, which were further visualized using a nomogram. Finally, calibration curve, C-index, and decision curve analysis (DCA) were applied to assess the performance of the different staging systems. RESULTS: A total of 5384 patients with ASCC were analyzed, revealing superior discrimination OS by the TNM9th edition compared to that by the TNM8th edition. Multivariate analysis identified the T and N stages as significant OS predictors (all p < 0.001). However, ambiguity persisted in stage III subgroups within the TNM9th edition, showing OS times of 102 months for stage IIIA disease, 88 months for stage IIIB disease, and 128 months for stage IIIC disease (all p > 0.05). Correlation analysis demonstrated an increased correlation for the T stage between the TNM8th and 9th editions (ρ value from 0.7 to 0.89), while the N stage correlation decreased (ρ value from 0.84 to 0.56). VIA and the prognostic nomogram highlighted the greater importance of the T stage over the N stage. Based on these findings, a new staging system was developed, and its clinical utility was confirmed through calibration curves, C-index values (from 0.598 to 0.604), and DCAs. CONCLUSIONS: Our new staging system exhibited slightly better prognostic value compared to the TNM9th staging systems for nonmetastatic ASCC and warrants further validation.

[Application of Photoplethysmography Combined with Deep Learning in Postoperative Monitoring of Flaps].

Objective: Photoelectric volumetric tracing (PPG) exhibits high sensitivity and specificity in flap monitoring. Deep learning (DL) is capable of automatically and robustly extracting features from raw data. In this study, we propose combining PPG with 1D convolutional neural networks (1D-CNN) to preliminarily explore the method's ability to distinguish the degree of embolism and to localize the embolic site in skin flap arteries. Methods: Data were collected under normal conditions and various embolic scenarios by creating vascular emboli in a dermatome artery model and a rabbit dermatome model. These datasets were then trained, validated, and tested using 1D-CNN. Results: As the degree of arterial embolization increased, the PPG amplitude upstream of the embolization site progressively increased, while the downstream amplitude progressively decreased, and the gap between the upstream and downstream amplitudes at the embolization site progressively widened. 1D-CNN was evaluated in the skin flap arterial model and rabbit skin flap model, achieving average accuracies of 98.36% and 95.90%, respectively. Conclusion: The combined monitoring approach of DL and PPG can effectively identify the degree of embolism and locate the embolic site within the skin flap artery.

[Sexual therapy combined with physical methods for the treatment of primary intravaginal anejaculation].

OBJECTIVE: To explore the clinical effect of sexual therapy combined with physical methods in the treatment of primary intravaginal anejaculation (PIAE) and its possible action mechanism. METHODS: Ninety PIAE patients with anxiety symptoms were equally randomized into three groups and treated by sexual therapy combined with vacuum negative pressure hydro pneumatic / pneumatic bubble massage (group A), sexual therapy (group B) or (vacuum negative pressure hydro pneumatic / pneumatic bubble massage (group C). After 15 cycles of treatment, the therapeutic effects were compared among the three groups of patients. RESULTS: The effectiveness rates in groups A, B and C were 86.67%, 46.67% and 30.00%, respectively, with statistically significant differences in the total effectiveness rate, the effective rate of the treatment of anxiety symptoms of the patients and their partners, and the effectiveness rate of the treatment of idiosyncratic masturbation (P<0.05). Pairwise comparison showed that the total effectiveness rate was dramatically higher in group A than in groups B and C (P<0.01), with no statistically significant difference between the latter two groups (P>0.05), that the effectiveness rate of the treatment of anxiety symptoms of the patients and sexual partners was remarkably higher in groups A and B than in C (P<0.01), with no statistically significant difference between the former two groups (P>0.05), and that the effectiveness rate of the treatment of idiosyncratic masturbation was significantly higher in group A than in B and C (P< 0.01), with no statistically significant difference between the latter two (P>0.05). CONCLUSION: PIAE is often accompanied by negative psychological state of the patients and their partners and idiosyncratic masturbation, which responds well to sexual therapy combined with vacuum negative pressure hydro pneumatic / pneumatic bubble massage.